Dummy Age/sex : xxxY / M 00000000 … : Dummy Age/sex : xxxY / M Lab No : 00000000 Rep centre : xxxxxxxxxxxxxxxxxxxxx Ref by : xxxxxxxxxxxxxxxxxxxxx Rec. Date : xx/xx/xxxx Rep Date

Name : Dummy Age/sex : xxxY / M

Lab No : 00000000

Rep centre : xxxxxxxxxxxxxxxxxxxxx Ref by : xxxxxxxxxxxxxxxxxxxxx

Rec. Date : xx/xx/xxxx Rep Date : xx/xx/xxxx

GENETIC MAPPING FOR WHOLE GENOME

(SNP genotyping using microarray)

TRAITS

TRAITS INFERENCE

ADIPONECTIN LEVELS Slightly high risk for reduced adiponectin levels

ALCOHOLISM Slightly high risk for alcoholism

ALCOHOL FLUSH REACTION Low risk for alcohol flushing

BLOOD PRESSURE Slightly high risk for hypertension/high blood pressure

BMI/OBESITY Low risk for obesity

BONE MINERAL DENSITY Low risk for osteoporosis; regular bone mineral density

CAFFEINE CONSUMPTION Low caffeine consumption

HDL CHOLESTEROL LEVELS Slightly high likelihood for increased levels of HDL-C

LDL CHOLESTEROL LEVELS Typical likelihood for optimal LDL -C level

DIET RECOMMENDATION Low fat diet recommended

EYE COLOUR

Likely to have darker shade of eye colour (brown / dark

brown / black)

compared to lighter shade (blue)

HOMOCYSTEINE LEVELS Low risk for increased homocysteine levels

NICOTINE DEPENDENCE Slightly high risk for nicotine dependence

PSA LEVELS PSA levels may be moderately higher than the general

population

TRIGLYCERIDE LEVELS Slightly high risk for hypertriglyceridemia

SPORTS & FITNESS Genetic advantage for sprint/power athletics

DISEASES

For diseases, we measure genetic risk as life time risk (LTR) and compare it with average life time risk

(Average LTR) of the population. The tables below show these details along with inferences.

DIABETES

CONDITION LTR AVERAGE LTR INFERENCE

TYPE 1 DIABETES 1.333% 1% High risk

TYPE 2 DIABETES 39.623% 20% High risk

CARDIOVASCULAR DISEASES


ATRIAL FIBRILLATION 2.527% 2% Medium risk

MYOCARDIAL INFARCTION 0.179% 0.19% Normal risk

CORONARY HEART DISEASE 0.706% 0.8% Normal risk

SUDDEN CARDIAC ARREST NA NA Normal risk

STROKE 0.228% 0.14% High risk

HEART FAILURE 1.421 % 1.5% Normal risk

LONG QT 0.09% 0.03% High risk

ENDOCRINE & REPRODUCTIVE


HYPOTHYROIDISM 0.288% 0.35% Normal risk CANCER

CONDITION LTR AVERAGE LTR INFERENCE PROSTATE CANCER 12.661% 15.5% Normal risk

TESTICULAR CANCER 2.715% 1.9% High risk

MELANOMA 0.679% 3.8% Normal risk

BLADDER CANCER 4.424% 5.2% Normal risk

COLORECTAL CANCER 12.621% 13.6% Normal risk

PANCREATIC CANCER 0.48% 0.6% Normal risk

RENAL CELL CARCINOMA 2.835% 3% Normal risk

LUNG CANCER 6.353% 7.5% Normal risk

THYROID CANCER 1.31% 2.3% Normal risk

BASAL CELL CARCINOMA 0.116% 0.12% Normal risk

CHRONIC LYMPHOCYTIC

LEUKEMIA

0.002% 0.005% Normal risk

HODGKIN'S LYMPHOMA 0.301% 0.7% Normal risk

FOLLICULAR LYMPHOMA 0.003% 0.0028% Normal risk

NEURO/PSYCHIATRIC


ALZHEIMER'S DISEASE 1.791% 6.2% Normal risk

AMYOTROPHIC LATERAL

SCLEROSIS

0.38% 0.5% Normal risk

BIPOLAR DISORDER 0.325% 1% Normal risk

MAJOR DEPRESSIVE DISORDER 6.016% 6.4% Normal risk

MIGRAINE 15.298% 14% Normal risk

MULTIPLE SCLEROSIS 0.02% 0.07% Normal risk

PARKINSON'S 0.124% 0.1% Medium risk

RESTLESS LEGS SYNDROME 2.826% 6% Normal risk

SCHIZOPHRENIA 0.502% 0.78% Normal risk

LIVER, GASTRO, & RENAL HEALTH

CONDITION LTR AVERAGE LTR INFERENCE BILIARY CIRRHOSIS 0.02% 0.0135% High risk

CELIAC DISEASE 0.478% 1% Normal risk

CHRONIC KIDNEY DISEASE 7.254% 8% Normal risk

CROHN'S DISEASE 0.024% 0.054% Normal risk

ULCERATIVE COLITIS 0.264% 0.505% Normal risk

BONES & JOINTS

CONDITION LTR AVERAGE LTR INFERENCE ANKYLOSING SPONDYLITIS 0.364% 0.4% Normal risk

OSTEOARTHRITIS 5.349% 4.5% Medium risk

RHEUMATOID ARTHRITIS 0.111% 0.8% Normal risk

RESPIRATORY


ASTHMA 9.757% 5.28% High risk AUTOIMMUNE

CONDITION LTR AVERAGE LTR INFERENCE LUPUS 0.006% 0.0125% Normal risk EYES

CONDITION LTR AVERAGE LTR INFERENCE GLAUCOMA 1.321% 2% Normal risk

AGE RELATED MACULAR DEGENERATION 52.099%

17%

High risk

SKIN

TRAITS

TRAITS INFERENCE

FRECKLES Low likelihood for skin / facial freckling

TANNING Slightly susceptible to tanning

SKIN PIGMENTATION Slightly high likelihood for lighter skin

HAIR COLOUR

Likely to have darker shade of hair colour (brown / dark brown / black)

compared to lighter hair shade (blonde or red)

HAIR TEXTURE Low likelihood for straight hairs

SUNBURNS Low likelihood for sunburns

EYE COLOUR

Likely to have darker shade of eye colour (brown / dark brown / black)

compared to lighter shade (blue)

CONDITIONS

CONDITION LTR AVERAGE LTR INFERENCE ATOPIC DERMATITIS 23.478% 19% Medium risk

PSORIASIS 0.838% 2.5% Normal risk

VITILIGO 0.51% 0.5% Normal risk

MALE PATTERN BALDNESS 21.8% 50% Normal risk

CANCERS

CONDITION LTR AVERAGE LTR INFERENCE MELANOMA 0.679% 3.8% Normal risk

SKIN CANCER (NONMELANOMA) NA NA Typical likelihood for

non-melanoma cancer

BASAL CELL CARCINOMA 0.116% 0.12% Normal risk

INHERITED CONDITIONS

TRAITS INFERENCE

G6PD DEFICIENCY

You do not have variants for G6PD enzyme deficiency and hence may not be at

risk for hemolytic anaemia when exposed to certain medications or food groups

PHENYLKETONURIA

You do not have variants for Phenylketonuria. Hence you may not be a carrier for

disease phenotype - Phenylketonuria

DRUG RESPONSES

TRAITS INFERENCE

5FU Low risk for drug induced toxicity.

ABACAVIR Low risk for drug induced toxicity.

ASPIRIN No significant risk reduction of CVD with Aspirin therapy.

CLOPIDOGREL Intermediate metabolizer. Reduced drug absorption. Therapy inefficient.

FLUCLOXACILLIN Low risk for drug induced liver toxicity.

METFORMIN High likelihood for positive drug response.

THIOPURINES High enzyme activity. Low risk for drug induced toxicity.

SIMVASTATIN Low risk for drug induced toxicity.

WARFARIN Low risk for drug sensitivity.

Note: Test does not prescribe or suggest any kind of medication to its customers. The "Drug Responses"

here refer to your genetic predisposition to the drugs mentioned in the report. This section is for a

physician's reference.

TRAITS

BLOOD PRESSURE Normal resting blood pressure for an adult is 120/80 mmHg. Blood pressure higher than normal is called hypertension (high BP), and high BP is said to be present if it is persistently at or above 140/90 mmHg. Genetics High blood pressure (or hypertension) is a polygenic trait (determined by multiple gene loci). Research has revealed over 10 genetic variants associated with at least 0.5mmHg increase in blood pressure (systolic or diastolic). Although the effect of each of these variants on blood pressure is not remarkable, the collective effect of several such implicated genetic variations make a significant impact on the phenotype of the individual. Point mutations on STK39 (chromosome 2) and CSK (chromosome 15) genes are identified with increased risk for high blood pressure. Additionally single base variations on 15q26.2, located in the intermediate region of RPL39P10-CHRM3 genes, 4q21.21 and 1q43 are also of greater significance with high blood pressure. Your Genetic Profile for Blood Pressure

Loci Marker Genotype Inference

LOCl00l32798 rs2398162 AA Slightly high risk for

hypertension/high blood

pressure CSK rs1378942 CC 4q21.21 rs16998073 TT

Note: There could be other variants, not screened by this test.

Complications This is a risk factor for stroke, heart attack, heart failure, peripheral arterial disease, kidney disease and other problems. Risk Factors Potential risk factors for hypertension include: Family history: Hypertension is highly inheritable and is most likely to pass on to offspring. Hence, genetic factors form one of the key components in determining the risk of high blood pressure. Age: Increasing age increases the risk for hypertension and heart disease. High rates of diastolic blood pressure are seen in men of 30-40 years, whereas in women hypertension is often associated after menopause. Sex: Although there is an equal risk of hypertension in both sexes, younger men and older women are most likely to be affected.

Diet: Diet rich in salt or sodium increases the blood pressure as it imposes water retention in kidneys, thereby affecting regular function of the body. Obesity: High body mass index contributes to direct increase in risk for hypertension. According to a study, decrease in body weight by 1 kg correlated with reduction of systolic and diastolic blood pressure by over 1.0 mmHg. Life style: Physical or mental pressure in routine life adds to the potential risk. Smoking and heavy alcohol addiction show direct correlation with high blood pressure. ADIPONECTIN LEVELS Adiponectin is an adipocyte (fat cell) derived plasma protein, also known as the 'starvation hormone'. It modulates a number of metabolic processes, including glucose regulation and fatty acid oxidation. Genetics Adiponectin is secreted by the white and brown adipose tissue in our body. ADIPOQ gene regulates the production of the hormone in the tissue. Genetic variation in ADIPOQ therefore directly affects the secretion of the hormone. Reduced adiponectin level in the body is correlated with serious medical conditions such as type 2 diabetes or associated phenotypes such as obesity, insulin resistance and many more. Hence, the gene is widely referred to determine the hormone level in the body. Your Genetic Profile for Adiponectin Levels


ADIPOQ

rs6773957

AG Slightly high risk for

reduced adiponectin

levels Note: There could be other variants, not screened by this test.

Complications Levels of this hormone could affect many clinical parameters such as blood glucose, indices of insulin resistance, proatherogenic dyslipidemia, and risk of type 2 diabetes, stroke, coronary artery disease and cancer. Many studies have shown that higher levels of adiponectin are protective as they lower the risk of type 2 diabetes and heart disease, whereas lower levels are associated with increased obesity and related comorbidities. Risk Factors Many studies have proved moderate to high estimates of heritability (30-70%) for plasma adiponectin levels. Other factors affecting plasma adiponectin levels include ‘body mass index’ or weight of an individual, where the association forms an inverse correlation between the two factors. Similar association is observed with other potential risk factors for low adiponectin levels such as diabetes, coronary artery disease and serum triglyceride concentration in the body. However, increased HDL-Cholesterol levels are associated with increase in hormone concentration in the body. BODY MASS INDEX / OBESITY

Body mass is measured using Body Mass Index (BMI), which is the best estimate of a person's body fat based on individual’s weight and height. Body mass index is defined as the individual's body mass divided by the square of his or her height and expressed in units kg/m2.

Ideal Adult BMI WHO Classification <18.5 Underweight 18.5-24.5 Normal

>25 Overweight >30 Obese Genetics Family studies, linkage analysis, twin studies and genome wide association data indicate that genetic framework of an individual contributes significantly to weight related phenotype like body mass index. Hereditary factors account for nearly 60% of variability for obesity, globally. Genes of appetite regulation and energy homeostasis like those involved in leptin-melanocortin pathway form direct correlation with body weight. However, genome wide association studies have tagged over 25 genetic variants related to obesity with a significant odds ratio of greater than 1.12. Melanocortin-4 receptor’ (MC4R) gene located on chromosome 18, and ‘fat mass and obesityassociated’ (FTO) gene on chromosome 16 are often studied to determine the person’s risk for obesity. The two genes were correlated with obesity in polycystic ovary syndrome and the latter is often associated with early onset obesity. Your Genetic Profile for BMI


FTO rs9939609 TT Low risk for obesity

FTO rs6499640 GG

MC4R rs10871777 AG

MC4R rs12970134 AG


Complications The higher the BMI (above 30), the greater the risk of incurring heart disease, high blood pressure, type 2 diabetes, gallstones, high blood pressure, stroke, abnormal blood fats, certain cancers, sleep apnea, obesity hypoventilation syndrome (breathing disorder), reproductive problems, and osteoarthritis. Risk Factors Obesity usually results from a combination of causes and contributing factors. Genetics: Genes may affect the amount and where the body fat is stored and distributed. They also play a role in how efficiently body converts food into energy and burns excess calories. Even when someone has a genetic predisposition (vary 40-70%), environmental factors influence gaining weight. Family lifestyle: Obesity tends to run in families because of similar eating, lifestyle, and activity habits. If one or both of the parents are obese, risk of children being obese increases. Diet and Lifestyle: Sedentary lifestyle and unhealthy diet lack of sleep also causes obesity. Smoking cessation: Increases weight, but in long run it gives benefit to your health than continuing. Medications: Certain medications like anti depressants, anti-seizure, anti-diabetes drugs, antipsychotics, steroids, beta blockers, and certain oral contraceptives are likely to increase weight.

Medical Problems: Prader-Willi syndrome, Cushing syndrome, Arthritis. CHOLESTEROL LEVELS Cholesterol is a fat-like substance found in all cells of the body and is required for membrane function and fluidity. Cholesterol serves as a precursor for the biosynthesis of steroid hormones, bile acids, and vitamin D. It travels through bloodstream in small packages called lipoproteins. Two kinds of lipoproteins carry cholesterol throughout our body, low-density lipoproteins (LDL) and high-density lipoproteins (HDL). Having healthy levels of both types of lipoproteins is important. High blood cholesterol is a condition in which one has too much cholesterol in blood. Genetics Genetic factors account for nearly 40% of cholesterol concentration in the body. External factors (environment and lifestyle) hold the rest of the proportion. Familial hypercholesterolemia is an inherited condition characterized by high levels of plasma cholesterol (particularly LDL) in the body. Apolipoprotein family of genes such as ‘APOB’ and ‘APOC1’ are known to influence LDL-C concentration in the body. Genetic variations in these genes or their regulatory regions cause hypercholesterolemia and particularly increase the plasma LDL-C levels. These genes are also associated with higher risk for heart diseases. On the other hand, variants on LDLR gene (LDL receptor) correlate with decreased LDL-C level. Specific beneficial variations on chromosome 8, 16 and 18 are known to increase HDL-C level in the body. It is identified that variants on chromosomes 8p21.3 and 18q21.1 are known to increase HDL-C level by 1.5mg/dl. Furthermore, variants of TBL2 gene on chromosome 7 also contribute to high HDL-C. Your Genetic Profile for Cholesterol Levels Markers for LDL cholesterol levels:


APOC1 rs4420638 AA Typical likelihood for optimal

LDL -C level APOB rs1367117 GG

LDLR rs6511720 CC

Markers for HDL cholesterol levels:


8p21.3 rs12678919 AA Slightly high likelihood

for increased levels of

HDL-C NUTF2 rs2271293 GG

16q13 rs3764261 AC

18q21.1 rs4939883 GG

HNF4A rs1800961 GG


Complications

Although cholesterol is important for human health, high levels of cholesterol in blood causes damage

to arteries and cardiovascular disease. Higher the level of HDL cholesterol blood, the lower is the chance

of getting heart disease. Higher the level of LDL cholesterol in blood, higher is the chance of getting

heart disease.

Risk Factors

Research has proved that both genes and diet influence cholesterol levels. Familial hypercholesteraemia

is an inherited condition, characterized by increased level of LDL - cholesterol.

TRIGLYCERIDE LEVELS

Triglycerides are fat molecules in the bloodstream that provide energy to various parts of the body.

Triglycerides are produced by the body and obtained from diet.

Genetics

Certain genetic variations can account for high triglyceride levels. Studies have identified variants on

ZNF259 gene to be associated with high triglyceride levels. Presence of 2 risk alleles at ‘rs964184’ of

ZNF259 gene is associated with at least two times higher risk of high triglyceride levels.

Your Genetic Profile for Triglyceride Levels


TBL2 rs17145738 GG Slightly high risk for

hypertriglyceridemia GALNT2 rs4846914 AG

ZNF259 rs964184 CG


Complications

High triglyceride levels may lead to an increased risk of atherosclerosis that can contribute to

cardiovascular diseases. However, studies reveal that triglyceride levels are not independent risk factors

of heart disease. They also indicate conditions that are likely to lead to high blood pressure, high blood

sugar, and high cholesterol levels.

Risk Factors Risk factors include: Gender: Some studies suggest that women are at a higher risk for increased triglyceride levels and the resulting complications. Other conditions: Often high triglyceride levels are side effects of conditions such as hypothyroidism, liver damage, type 2 diabetes, or kidney diseases. Lifestyle: Diet rich in fats, sedentary habits, and lack of exercise have been found to increase the risk of high triglyceride levels. Genetics: Genetic variations can also account for high triglyceride levels. Genetic factors affecting the

levels may vary across individuals. Studies have identified few common genes in these cases. HOMOCYSTEINE LEVELS Homocysteine is a common amino acid found in the blood and is acquired mostly from eating methionine rich foods like meat, fish, and dairy products. Vitamin B6 (pyridoxine), vitamin B12, and folic

acid are needed to help these reactions occur. Methionine undergoes a terminal methyl transfer reaction to form Homocysteine molecule. Ideally, optimal homocysteine levels are close to 7-8 μmol/L. Genetics A well established MTHFR variation known to cause an amino acid change of Ala222Val in the enzyme leads to reduced enzyme activity. This affects the conversion of homocysteines leading to the metabolite accumulation in the body. The marker is associated with susceptibility to neural tube defects, colon cancer etc. Many studies have reported a notable association of MTHFR gene variation to Hyperhomocysteinemia. However, its correlation with CVD is not statistically significant. Your Genetic Profile for Homocysteine Levels


MTHFR

rs1801133

GG

Low risk for increased

homocysteine levels Note: There could be other variants, not screened by this test.

Complications Increased homocysteine levels in the body lead to a condition called Hyperhomocysteinemia. Studies indicate that hyperhomocysteinemia is associated with higher risk of heart diseases and stroke among general population. Enhanced homocysteine in the body can act as an independent risk factor for CVD. Associate evidences for hyperhomocysteinemia with cognitive dysfunctions (Alzheimer's disease, dementia, schizophrenia) are also reported. Homocysteinuria is a condition where homocysteine level in blood and urine reaches up to 100-400 μmol/L. This is an extreme condition of metabolite accumulation and the patient is generally treated with heavy doses of vitamin therapy. Enhanced homocysteine levels may increase the risk of osteoporosis, cerebrovascular disease or kidney diseases. Risk Factors Many studies have reported notable association of MTHFR gene variation to hyperhomocysteinemia. However, its correlation with CVD is not statistically significant. Globally, South Asians and Europeans are known to have increased homocysteine levels. BONE MINERAL DENSITY Bone mineral density (BMD) or bone density measures how much calcium and other types of minerals are in an area of bone. BMD is used as an indicator of osteoporosis and predicts the risk of bone fracture. Genetics Several environmental and genetic factors trigger osteoporotic fractures or determine bone mineral density in individuals. Although bones turn fragile with increasing age, heritability factors also account for disease outcome, to a considerable extent. There are over 20 genome wide association studies reporting nearly 100 genetic markers for osteoporosis related traits. However, the association of these markers with precise causative mechanism of reduction in bone mineral density is yet to be defined. WNT4 – ZBTB40 loci on chromosome 1, RANKL region on chromosome 13 and LRP5 region on chromosome 11 are widely reported to be associated with a greater risk (over 1.2 times) of developing osteoporotic fractures. Your Genetic Profile for BMD


WNT4 – ZBTB40 rs7524102 AG Low risk for

osteoporosis; regular

bone mineral density RANKL rs9594738 GG

LRP5 rs4988321 GG

LRP5 rs3736228 GG


Complications Bones are made of a mineral and protein scaffold filled with bone cells. Bone is continually broken down and replaced. When the rate of bone loss outpaces the rate of replacement, bones weaken, eventually leading to osteoporosis and increased risk of fracture. Low bone density (Osteopenia) increases the risk of osteoporosis and fracture. Risk Factors Many factors, including age, menopausal status, smoking, physical activity, diet, coexisting diseases, and pharmacologic treatments influence the risk of osteoporosis; however, one of the most clinically important risk factors is a family history of the disorder. Many studies have suggested that genetic differences may account for more than half the variance in bone mineral density between people. PSA LEVELS Prostate specific antigen (PSA), is a protease also known as kallikrein-related peptidase. This enzyme is produced by cells of the prostate gland and is thought to be involved in liquefaction of seminal coagulum and helps in the sperm movement. The level of PSA in blood of a normal person is very low. But the levels of this antigen is known to be elevated in men with prostate cancer prostatitis (inflammation of the prostate) and benign prostatic hyperplasia (enlargement of the prostate) and urinary tract infections. This antigen is used as a biomarker for prostate cancer. Serum level of PSA is useful in the diagnosis and monitoring of prostatic carcinoma. Genetics MSMB gene encodes a protein which belongs to a immunoglobulin binding factor family. It is synthesized by the epithelial cells of the prostate gland and secreted into the seminal plasma. This protein has inhibin-like activity. Studies have proved that functional variant in this gene is associated with increased PSA levels and prostate cancer.


FGFR2 rs10788160 GG PSA levels may be moderately

higher than the general

population MSMB rs10993994 AA

TBX3 rs11067228 GG

TERT rs401681 GG

HNF1B rs4430796 AA

Complications The levels of PSA can range from 1ng/ml to hundreds of ng/ml. A raised PSA level always may not be suggestive of prostate cancer, but indicates a problem related to prostate.

Age of males Elevated PSA Range

50-59 years PSA level is considered elevated if it is 3ng/ml or

higher.

60-69 years

PSA level is considered elevated if it is 4ng/ml or

higher.

70 or above PSA level is elevated if it is 5ng/ml or higher. ALCOHOLISM Alcoholism or alcohol dependence is a chronic, progressive disease where victims become “addicted” to alcohol and face severe repercussions while trying to give up. Genetics Specific genetic loci correlate with alcohol dependency. Identifying such markers will only aid in screening for potential alcohol dependent candidates. They can then take necessary measures at an earlier stage in order to avoid addiction. The chromosome region 2q35, and genes like ANKK1 and OPRM1 in human genome are linked to alcohol dependency related characteristics. In some cases, alcohol intoxication may lead to development of brain seizures, after few hours of alcohol cessation. Most commonly, the cerebral cortex of the brain is affected causing motor seizures. Many research reports have identified the marker on SLC6A3 gene to be associated with the risk of severe alcohol withdrawal seizures in alcohol dependent subjects. Higher tolerance to alcohol or alcohol abuse can manifest into mental disorder of DSM-IV category. Your Genetic Profile for Alcoholism


2q35 rs7590720 AA Slightly high risk for

alcoholism OPRM1 rs1799971 GG

ANKK1 rs1800497 AG


Complications Alcoholism leads to anemia, cancer, CVD, cirrhosis of liver, dementia, depression, pancreatitis, and many other complications.Excessive drinking can cause erectile dysfunction in men. In women, it can interrupt menstrual cycle. Alcohol use during pregnancy causes fetal alcohol syndrome, resulting physical and developmental problems that last a lifetime. On a long run, heavy drinking can cause involuntary rapid eye movement (nystagmus) as well as weakness and paralysis of eye muscles due to a deficiency of vitamin B-1 (thiamine). Excessive drinking can affect nervous system, causing numbness and pain in hands and feet, disordered thinking, dementia and short-term memory loss. Weakened immune system: alcoholism can make it harder for your body to resist disease, making you more susceptible to illnesses. Increased risk of cancer: Long-term excessive alcohol use has been linked to a higher risk for many cancers, including mouth, throat, liver, colon and breast cancer. Even moderate drinking can increase the risk of breast cancer. It is no wonder that the World Health Organization purports alcohol as the world’s third largest risk factor for disease burden – the leading factor in the US and Western Pacific and the second largest in Europe. Alcohol compromises individual health, domestic harmony and societal welfare, sometimes leading to dire consequences.

Risk Factors Researchers have identified many risk factors for alcoholism: Alcohol Habit: People who consume alcohol steadily over time or indulge in binge drinking on a regular basis are purported to be at a greater risk of becoming alcoholics. Gender: Research suggests that men are at a higher risk of becoming alcohol dependant, while women are at a higher risk of developing complications related to alcoholism. Age: People who start consuming alcohol at a younger age are more likely to become alcohol dependent. Genetics: Research suggests that genes contribute to 50-60% of the risk of alcoholism. Family history: Family environment can increase the risk of alcoholism. Children whose parents are alcoholic, indulge in alcohol or substance abuse, have psychological problems, or indulge in violence after consuming alcohol are at a higher risk of alcoholism. Mental health problems: People with mental health problems such as depression or anxiety are at a higher risk of alcoholism. Social and cultural factors: Peer pressure, a partner’s indulgence in alcohol, and the glamorous portrayal of alcohol in the media are some factors known to increase risk of alcohol dependence. ALCOHOL FLUSH REACTION Alcohol flush reaction is a condition where people experience flushes or blotches on the face and body when they consume alcohol. This is a result of acetaldehyde accumulation during alcohol metabolism. Often, the ungainly effects of alcohol consumption in people who show this reaction contribute to lower alcoholism. Genetics Research indicates correlation between rs671 allelle on ALDH2 gene and alcohol flush reaction.


ALDH2

rs671

GG

Low risk for alcohol

flushing Note: There could be other variants, not screened by this test.

Complications Immediate effects may include blotchy and flushed skin, nausea and increased heart rate. This condition is associated with increased risk for esophageal cancer, even among those who report moderate alcohol consumption. Risk factors Genetics: This condition is associated with a genotype of rs671 allelle on ALDH2 gene. Geography: Prevalence is more among East Asians. NICOTINE DEPENDENCE Smoking is one of the major causes of lung cancer, and globally, one of the most lethal habits found in the young/adult population. Tobacco use has prevailed for centuries, and remains highly prevalent in developing/developed countries as well. The addictive nature of nicotine (chief constituent in tobacco) makes smoking a recurrent habit in both men and women.

Smoking behavior has different aspects, some of which are:

Nicotine Dependence i.e., ND (measured by CPD (cigarettes per day) and TTF (Time To First cigarette)

(or) ever versus never smokers Smoking Initiation/Onset age

Smoking Cessation (or) former versus current smokers Since smoking is defined as the usage and intake of tobacco and tobacco-containing products (cigars/

pipe etc), nicotine dependence is the primary determinant of smoking behavior. Nicotine exerts a

pleasurable effect, as it crosses the Blood-Brain Barrier (BBB) within minutes of having a cigarette. As the

feeling is short-lived, more cigarettes are lit and addiction quickly develops. Genetics Smoking behavior develops mostly through environmental influences, but the heritability of initiation, persistence, smoking quantity and addiction is quite high, according to several studies. A cluster of genes that relate to nicotinic acetylcholine receptors (nAChR) have been repeatedly investigated for their role in smoking risk. These are present primarily in areas related to cognitive function (cortex, ganglia). Nicotine activates the nACh receptors to release neurotransmitters such as acetylcholine, dopamine, serotonin and glutamate that produces the smoking euphoria. Some of these variants contribute to lung cancer risk in different populations, as well. Your Genetic Profile for Nicotine Dependence


CHRNA5 rs16969968 AG Slightly high risk for nicotine

dependence CHRNA3 rs578776 AG

CHRNA3 rs6495308 AG


Withdrawal symptoms Nicotine users who are heavily addicted are more likely to experience withdrawal symptoms- anxiety/ restlessness, craving for nicotine, disturbed sleep, headaches and depression. Health complications Nicotine intake releases dopamine and norepinephrine (chemical molecules called neurotransmitters), and hence, a neurologically stimulated sensation of pleasure is experienced. Since nicotine is the chief constituent of tobacco, higher addiction to nicotine will lead to increased tobacco consumption. This inadvertently results in the complications which are caused by the chemicals in tobacco, and thereby, reduced quality of life. The negative health effects of prolonged exposure to tobacco smoke include increased risk of cancers (lung, head and neck, bladder, pancreas, kidney and cervix, and some types of leukemia), CVDs, chronic obstructive pulmonary diseases, diabetes, infertility and impotence, and weakened senses. Exposure to environmental tobacco smoke also increases the risk of these diseases. CAFFEINE CONSUMPTION Caffeinated beverages and foods (e.g., coffee, tea and cocoa drinks) are consumed by ~80-90% of the global population. However, the frequency of intake, number of cups per day and/or units consumed varies across all ages. This is explained by differing caffeine sensitivity and metabolic response, due to genetic factors (apart from environmental influences and social habits). Genetics CYP1A2 encodes cytochrome P450 A2 protein, which is the primary enzyme in caffeine metabolism in the liver (~95%). Genetic variants in this gene have been proved to alter caffeine habits, across various

populations. Adenosine receptors, A1 and A2A act as antagonists and mediate the biological effect of caffeine on the CNS. AHR (aryl hydrocarbon receptor) is responsible for xenobiotic compound metabolism, such as those found in roasted coffee and induces the transcription of CYP1A1/A2 enzymes, and is a known factor that influences caffeine consumption. Other important genes include NRCAM (neuronal cell adhesion molecule) that causes vulnerability to addiction and ULK3 (Unc-51-Like Kinase 3), which regulates sonic hedgehog signalling and autophagy. Your Genetic Profile for Caffeine Consumption


CYP1A1 rs2470893 GG Low caffeine

consumption CYP1A2 rs2472304 GG

CYP1A1/CYP1A2 rs2472297 GG

AHR rs6968865 AT

NRCAM rs382140 GG

AHR rs4410790 AG

ULK3 rs6495122 AA

SCAMP5,PPCDC rs12148488 AA

Effects of Caffeine Intake Caffeine is a potent drug that can develop addiction in the consumer. It is a strong stimulant that directly affects the central nervous system (CNS). For decades, the positive and negative effects of caffeine have been studied in different parts of the globe. Known advantages of caffeine (moderate intake/<200 mg/day) are:

Reduced risk for type-2 diabetes, Alzheimer's, Parkinson's and dementia

Reduced stress/enhanced mood

Antioxidant and stimulant function/increased alertness Known disadvantages of caffeine (higher intake/>200 mg/day) are:

Hypertension/increased blood pressure

Insomnia/sleep disorders

Possible pregnancy complications

Cancer risk (polycyclic aromatic hydrocarbons in roasted coffee are carcinogenic chemicals) DIET RECOMMENDATION Variation in eating behavior across people is driven by a combination of both genetic and environmental influences. Genetic factors play an important role in influencing hunger pangs, satiety after meals, metabolic rate and calorie requirements. This explains the predisposition of certain individuals to be leaner (or) overweight, even if they are on the same diet. Dietary intake affects the interaction between several major hormones and enzymes, thereby the overall lipid profile and body composition of an individual. Genetics

The hypothalamus (a part of the human brain) controls a majority of the bodily functions including food intake, weight and metabolism. Many genes associated with hypothalamic function have been studied or possible role in mechanisms underlying body weight regulation and food intake in individuals. Peroxisome proliferator-activated receptor GAMMA (PPARG) gene produces a protein that regulates fat storage. Presence of one PPARG variant increases the chances of a person to be overweight, by affecting the body's response to weight regulation under calorie restriction. Individuals with the ''risk'' variant of this gene typically accumulate more fat in their body, and hence are more likely to be overweight, if not on a restricted diet. Other genes that indirectly affect fat and body composition include FTO (fat mass and obesity) gene that has been linked strongly with body mass index, waist circumference and weight in many population based studies. This gene is expressed in adipose tissue, skeletal muscle and the brain. There is some speculation that energy intake and fasting glucose are also dependent on this gene. One of the FTO gene variants is linked with higher number of eating episodes per day. The presence of this genetic marker predisposes towards more frequent, calorie-rich meals and therefore, higher BMI and/or obesity. Animal model studies (mouse, rat) and genome wide studies in different human ethnicities have provided evidence for the same. Melanocortin-4 receptor (MC4R), ADIPOQ, and POMC are among the genes that modulate macronutrient (carbohydrate, fat and protein) consumption. Some of these genes are considered by us in determining an individual’s genetic predisposition for body mass index/obesity. Your Predisposed Diet Pattern

SNP Gene Symbol Chromosome Genotype Inference

rs1801282 PPARG 3 CG Low fat diet recommended


SPORTS & FITNESS Genetics play a significant role in determining sports performance of an individual. It is a polygenic trait and over 100 genes are reported to be correlated with physical phenotypes like muscle performance, endurance ability, muscle contraction force, cardiac performance, oxygen intake, etc. Genetic factors determine nearly 50% of variation in physical fitness across the globe. Additionally a number of environmental, psychological and social factors should all be favorable in expressing the appropriate phenotype. Right nutrition and proper sport training are vital factors that influence the performance. Body mass index is crucial in determining back muscle performance. Genetics Almost all genetic services determining general sports ability target the gene ACTN3 (alpha actinin 3) in the body. Many research articles have correlated ACTN3 gene with muscle performance in the general population. Functional ACTN3 gene is largely identified in elite or Olympic level athletes, sprinters and body builders, who harbor great potential of physical performance. In addition, it is seen that people with non-functional ACTN3 gene are very rare among elite athletes. The non-functional ACTN3 genotype constitutes around 2-3% of total population among elite athletes and is reported to be around 10 times greater in the general population. The gene ACTN3 belongs to the family of alpha actinins that are actin-binding proteins that maintain the cytoskeletal component in our body. The gene is specifically expressed in fast glycolytic skeletal muscle fibres that aid in muscle contraction activities like sprinting and weight lifting.

A common nonsense polymorphism (R577X) in the ACTN3 gene leads to deficiency in protein products, resulting in low muscle strength. However, R577X polymorphism in ACTN3 is correlated with increase in endurance performance in individuals, unlike the functional gene that corresponds to sprint performance. This non-functional variant of the gene is widely prevalent in Asians and is sparse among Caucasian and Africans. Genetic Testing in Sports All genetic tests that determine an individual’s or child’s innate potential in sports will only uncover a small fraction of genetic prerequisites, for an elite athlete. ACTN3 test will approximately account for only 3% of variation seen in muscle performance. Hence, the results should strictly not gauge the child’s potential or intervene in pursuing his/her career in sports. Predisposition to Athletic Performance


ACTN3

rs1815739

GG

Genetic advantage for

sprint/power athletics Note: There could be other variants, not screened by this test.

EYE COLOUR Many genetic studies have been conducted to unravel the factors determining eye colour in humans. Although it was once believed that eye colour follows conventional Mendelian pattern of inheritance, recent studies have indicated that the pigmentation trait involves multiple factors and complex mechanism. Eye colour technically refers to colour of iris (flat, circular structure) of the eye. Pigments within iris largely determine the eye colour. Generally, brown eyes and its related shades (dark brown to black) are widely prevalent across the globe. Green eye is relatively common in parts of Europe, Middle East, and Central Asia. On the other hand, blue eye colour is a recessive trait and is often exclusive to North European belt. Genetics Both brown and green eyes are dominant over blue, which means that the just a single copy (of two) of brown or green eye colour factor will express the corresponding colour. More specifically, brown eye is dominant over green eye colour. When brown and green factors are recessive in both the alleles the person is disposed to have lighter shades of pigmentation like blue eyes. This is because of significant reduction in the amount of melanin pigment, which decides the colour of one’s hair, eyes and skin. OCA2 gene produces P-protein in melanocytes. Melanocytes are cells that produce melanin pigment in the body. Genetic variation in OCA2 has a significant impact on melanin production, thus affecting the trait. Genetic segment present in the near upstream region of OCA2, specifically in the HERC2 locus, are reported to regulate the expression of OCA2 gene. Increase or decrease in the expression of OCA2 gene is partly controlled by this stretch of genetic sequence. Hence specific variants of HERC2 gene account for variation in the pigmentation. Your Genetic Profile for Eye Colour


HERC2

rs12913832

AA

Likely to have darker shade of eye colour (brown / dark brown /

black) compared to lighter shade (blue) Note: There could be other variants, not screened by this test.

DISEASES TYPE 1 DIABETES

Your risk Population average Your variant score 1.33x relative to average

population 1 in 100 4 out of 8

Type 1 diabetes mellitus, previously known as juvenile diabetes, is a chronic autoimmune disease* resulting in destruction of insulin producing beta cells of pancreas. Insulin plays a crucial role in meeting energy requirements of a human body by supplying glucose to, which in turn save and utilize this blood sugar (glucose) for energy. Type 1 diabetes is usually diagnosed in children and young adults, but it can affect people at any age. Once affected with this form of diabetes, the insulin producing beta cells of pancreas are completely destroyed within 5-10 years. *(Autoimmune disease is a condition where the person's immune system fails to distinguish between foreign and own cells resulting in immune response towards own cells and tissues.) Genetics Type 1 diabetes is predominantly a genetic disorder with its inheritability risk factor at 10% approximately. Being an autoimmune condition, it is widely accepted that HLA class 2 genes of chromosome 6 play a major role in the onset of this disease; but over time, many non-HLA genes are also identified and suspected to contribute equally to the risk. The genetic content, DNA (deoxyribonucleic acid) of your sample was analyzed and we identified some 'mutations' or changes that are associated with this medical condition. Details regarding 'mutations' or changes detected in your DNA are given below:

SNP ID Gene Chr. # Risk Allele Genotype rs1004446 IGF2;INS-IGF2 11 G AG rs12708716 CLEC16A 16 A AA

rs17696736 NAA25 12 G AA rs1990760 IFIH1 2 A AA

rs2476601 PTPN22 1 A GG rs6679677 RPS2P14 - RSBN1 1 A CC

rs7202877 CTRB2 - CTRB1 16 C AA

rs9272346 HLA-DQA1 6 G GG

Note: Genetic component of an individual form a minor fraction of the equation and are not the absolute causative

factors that determine the outcome. There could be several other influential elements acting simultaneously that

decide the final outcome of the condition.


Risk Factors Type 1 Diabetes is predominantly a genetic disorder that may be resultant of risk factors listed below Environment: Various environmental determinants are suspected to trigger and potentiate Type 1 Diabetes although contribution of any particular exogenous factor has not been proven yet. Chemicals and Drugs: Some chemicals that are accidentally ingested are known to specifically destroy pancreatic cells, thereby stopping normal insulin production. Even some cancer and antibiotic drugs taken as medication are known to kill pancreatic cells, resulting in loss of insulin production.

Chronic viral infection: Some viruses of Coxsackie virus family are known to trigger autoimmune response leading to destruction of beta cells of pancreas. This vulnerability towards virus is not common. Genetic factors: Type 1 Diabetes is a polygenic autoimmune disease with many different genes contributing to the risk leading to onset of Type 1 Diabetes. TYPE 2 DIABETES

Your risk Population average Your variant score 1.98x relative to average

population 1 in 5 9 out of 14

Type 2 diabetes or non-insulin dependent diabetes mellitus is the most common form of diabetes constituting 90% of the diabetic population and a chronic (lifelong) metabolic disorder, which is marked by high levels of sugar (glucose) in the blood. Type 2 diabetes is caused due to decreased insulin production or insulin resistance (reduced response to insulin). Normally, when we consume food glucose levels increase in blood. As a response to increased glucose levels, pancreas produces insulin hormone, which helps in glucose uptake in to cells and storage in liver for future use. However, when the body takes up too much of sugar rich foods, the blood glucose levels are drastically increased, triggering excess insulin production. In the long course, the body develops tolerance to increased insulin production and gradually fails to respond to insulin, which results in high level of glucose in blood, thereby causing problem is the circulation leading to complications like heart diseases, kidney problem (nephropathy), eye diseases (retinopathy), gangrene, etc. MMGGPK0615189|M| 7/10/2015| V 1.0 32 Genetics The genetics of type 2 diabetes is complicated, with many different genes influencing the risk of developing the disease. Numerous SNPs have been associated with genetic predisposition to diabetes. These set of SNPs, along with other factors (life style, environment, obesity, etc.) determine a person’s overall risk for developing diabetes. The genetic content, DNA (deoxyribonucleic acid) of your sample was analyzed and we identified some 'mutations' or changes that are associated with this medical condition. Details regarding 'mutations' or changes detected in your DNA are given below:

SNP ID Gene Chr. # Risk Allele Genotype

rs10811661 CDKN2B 9 G AA rs13266634 SLC30A8 8 G GG rs1801282 PPARG 3 G CG

rs2237892 KCNQ1 11 A GG rs4402960 IGF2BP2 3 A AC rs4712523 CDKAL1 6 G AA

rs5015480 HHEX - EXOC6 10 A AA

rs5219 KCNJ11 11 A AG

rs7901695 TCF7L2 10 G GG

rs7903146 TCF7L2 10 A AA

rs8050136 FTO 16 A CC

rs9300039 RPL9P23 - API5 11 A AC

rs9939609 FTO 16 A TT

rs1470579 IGF2BP2 3 C AC


factors that determine the outcome. There could be several other influential elements acting simultaneously that decide

the final outcome of the condition.


Risk Factors High familial aggregation: Several studies in India and abroad have shown that Indians have a genetic predisposition to diabetes, which gets easily unmasked when the environmental conditions are adverse. The fact that nearly 75% of the type 2 diabetic patients have first degree family history of diabetes indicates a strong familial aggregation in the Indian diabetic patients. Obesity especially central obesity: In several ethnic populations including the relatively non-obese South Indian population, the android pattern of body fat, typified by more upper body adiposity measured as waist hip ratio (WHR) was found to be a greater risk factor for type 2 diabetes than general obesity. Our studies have shown that central obesity is common in Indians despite low rates of obesity. The adverse effect of central obesity is manifested in increasing tertiles of BMI both in men and women, the effect being more evident in women. This is probably one of the reasons for a higher prevalence of diabetes in women in urban area Insulin resistance: Insulin resistance has been demonstrated to be a characteristic feature of Asian Indians. Comparison of Asian Indians, Europeans and other ethnic groups has shown that the former have higher insulin response than others, at fasting and in response to glucose. Lifestyle changes: The primary cause for diabetes is transition associated with changes in dietary patterns and decreased physical activity as evident from the higher prevalence of diabetes in the urban population. STROKE

Your risk Population average Your variant score

1.63x relative to population

average

7 in 500 2 out of 3

Stroke is a commonly used term for cerebrovascular accidents. It is a medical phenomenon where blood

supply to the brain is interrupted. As a result, the brain cells get damaged due to lack of oxygen and

nutrients. Any damage in blood vessels innervating the brain (blockage, rupture, hardening of blood

vessels, etc.) may disrupt blood supply to the brain. It may also lead to leakage of blood (hemorrhages) in

the brain. Loss of voluntary movement or inability to move the limbs, inability of speech and sight with

severe headache are some symptoms of the condition.

Genetics Apart from several modifiable and non-modifiable environmental factors that contribute to the development of Stroke, genetic factors constitute atleast 50% of the risk. The genetics of stroke is however very complex, as several physiological processes starting from blood clot formation to breakdown of emboli, could lead to increased risk of stroke. Several candidate gene analysis data and genome wide association data have identified variants in rs12425791 and rs2200733

to be associated with increased risk for stroke. Specific risk alleles in these SNPs have atleast 1.2 times greater risk for the condition.

SNP ID Gene Chr. # Risk Allele Genotype rs11984041 HDAC9 7 A GG rs12425791 NINJ2 12 A AA

rs2200733 PITX2 -

RPL36AP23 4 A AG





Risk Factors The risk for stroke increases with age. Men are more prone to develop ischemic stroke than women. Certain cancers, chronic kidney disease could trigger stroke. Many single gene autosomal dominant and recessive disorders , X-linked disorders are said to be associated with increased risk for stroke. LONG QT


3.01x 3 in 10000 2 out of 2 Long QT is a disorder in which abnormal electrical signals are generated in the heart. Electric impulses are necessary for the heart to contract and pump blood to the rest of the body. A single heart beat produces five distinct electric waves known as P, Q, R, S and T. The body controls the timing of each of these waves. Long QT is a medical condition in which the electric activity within the Q and T waves goes abnormally long and occurs in the lower chambers of the heart. Abnormal electric signals generated in the heart further lead to other medical complications like irregular heartbeat – known as ‘arrhythmia’. Most often long QT turns asymptomatic. Fainting, abnormal heart beat, and unexplained sudden cardiac arrest are observed in fatal cases of the condition. Genetics Several mutations associated with at least 10 different loci are known to correlate with long QT. Certain congenital genetic mutations have also been identified for the condition. On the other hand, one may acquire the condition in his/her lifetime, as a result of response to some medications etc. The presence of at least a single ‘A’ allele on rs12143842 (reverse orientation) or single ‘A’ allele on rs12029454 of NOS1AP gene are known to be associated with increased risk for long QT interval.

SNP ID Gene Chr. # Risk Allele Genotype rs12143842 NOS1AP 1 A AG

rs12029454 NOS1AP 1 A AG Note: There could be other variants, not screened by this test.



the final outcome of the condition. Risk Factors Those with other heart diseases and family history of long QT are at a higher risk of developing the condition. Certain medications may adversely affect the QT interval in the body. Eating disorders like anorexia nervosa may act as an additional risk component for long QT interval.

TESTICULAR CANCER


1.43x relative to average

population

19 in 1000 2 out of 3

Testicular cancer is a relatively rare form of cancer that affects testicles, which are part of the male reproductive system. Cancer may affect cells of 1 or both testicles. Although this type of cancer constitutes 1% of total cancer cases in men, it is the most common cancer seen in young men. Germ cell tumors of testis constitute over 90% of testicular cancers. Lumps, swelling or pain in groin area and testicles are common symptoms of testicular cancer. A feeling of heaviness in the lower abdomen is seen in few people. Genetics Although not much has been known to explain the molecular basis of testicular cancer, certain regions on chromosome 5, 6, 9 and 12 are proven for their association with testicular cancer. Genome wide association studies conducted on over 3000 testicular cancer cases collectively indicate important genes such as KITLG, BAK1, SPRY4, DMRT1 and TERT for their correlation with testicular cancer. The variants observed in some of these genes intervene in KIT signalling pathway that regulates the development of testicular germ cells. Nevertheless some variants on DMRT1 and KITLG are found to have protective effect against testicular cancer. Details regarding 'mutations' or changes detected in your DNA are given below:


rs4635969 TERT - CLPTM1L 5 A GG

rs210138 BAK1 6 G AG

rs4624820 SPRY4 5 A AA Note: Genetic component of an individual form a minor fraction of the equation and are not the absolute causative factors that determine the outcome. There could be several other influential elements acting simultaneously that decide the final outcome of the condition. Note: There could be other variants, not screened by this test. Risk Factors Gender: The disease occurs only in men. Age : Most often it affects young men with age group of 20 – 35 years. Birth defects: Abnormal testicle development or having undescended testicles (wherein the testicles fold within abdomen and do not descend into scrotum, by birth - technically referred as cryptorchidism) lead to higher risk of testicular cancer. Although undescended testicles are operated surgically to bring back to normal condition, the risk for testicular cancer continues to remain high as before. Family history: Individuals whose family, particularly brother, is affected with testicular cancer are at nearly 8-10 fold higher risk for developing the disease. However, the risk associated may be slightly lower as in 4-6 folds when the father is being affected. Nearly 1-3% of total testicular cancer cases account for familial inheritance. Ethnicity: In general, Asians and African Americans are at two times lower risk than whites. BILIARY CIRRHOSIS



population

135 in 1,00,00,000 2 out of 3

Primary biliary cirrhosis is a rare autoimmune liver disease characterized by self destruction of intrahepatic bile ducts (small channels for bile flow) causing cholestasis (obstruction in normal bile flow). It eventually results in fibrosis and scarring of liver tissue (cirrhosis), due to decreased bile secretion and toxin retention. Measurement of serum titers for antimitochondrial antibodies (AMAs) and histopathological analysis are performed during clinical diagnosis. AMAs are produced when the body loses its tolerance to pyruvate dehydrogenase complex (PDC-E2) subunit, which is found in biliary epithelial cells. This seems to be one of the mechanisms for PBC pathogenesis. Genetics IRF5-TNPO3 (interferon regulatory factor 5-transportin 3) gene, MMEL1 (membrane metalloendopeptidase–like 1) and SP1B (Spi-B transcription factor which regulates B-cell signalling and dendritic cell development) are among the other genes for PBC risk association. Replication studies in larger populations will establish their statistical relevance. Autoimmune disease-associated loci (such as Human Leukocyte Antigen (HLA) and Major Histocompatibility Complex (MHC) molecules) have been studied for PBC susceptibility and genetic risk. Other autoimmune diseases have already been linked with loci in this region. PTPN22 (protein tyrosine phosphatase 22), VDR (vitamin D receptor, for its role in immunomodulation) and IL-12 (interleukin cell signalling pathway gene) have been investigated for their possible genetic contribution to PBC risk. Further research is warranted on the same. The genetic content, DNA (deoxyribonucleic acid) of your sample was analyzed and we identified some 'mutations' or changes that are associated with this medical condition. Details regarding 'mutations' or changes detected in your DNA are given below:


rs10488631 IRF5 – TNPO3 7 G AA rs3748816 MMEL1 1 G GG

rs3745516 SPIB 19 A AG Note: Genetic component of an individual form a minor fraction of the equation and are not the absolute causative



Note: There could be other variants, not screened by this test. Risk Factors Gender: PBC has a female preponderance (~90% cases are women), with a female:male ratio of 9:1. Age: Typically, PBC is seen in middle-age (>40 years). Family history: First-degree relatives of PBC cases have an increased risk. Since it is more prevalent in middle-aged women, this disease clusters in mother-daughter or sister-sister pairs, in families. ASTHMA



population

1 in 20 7 out of 10

Asthma is a chronic respiratory disorder affecting the airways of lungs. It is characterized by recurrent attacks of breathlessness. The inside linings of airways swell because of inflammation, narrowing down the passage of airflow for lungs. As a result, the lungs are deprived of or receive less oxygen. Genetics Asthma is a complex genetic disorder involving interaction of many genes in combination. Single gene variation is less likely to correlate with the disease. Complex molecular level interactions involving various proteins along with environmental stimulants (protein–protein or protein–environment) together predict the individual's susceptibility levels. Linkage analysis, candidate gene and genome wide association studies have reported over hundred genes associated with biological relevance to asthma. However, not many have marked clinical level attention. Furthermore, genetic mutants may not show up phenotypically until triggered externally by various stimulants. Genetic variants associated with IL13, IL1RL1/IL18, IL33, IL2RB are known to correlate with the disease phenotype. Variants of SMAD3, HLA region and RAD50 are also some of those established variants of asthma. A lot of research is ongoing to discover potential molecular markers corresponding to the etiology of asthma. Genetic elements that are protective against asthma are also being searched. Furthermore, pharmacogenetics of asthma is also extensively studied to predict drug response of individuals being treated for asthma. The genetic content, DNA (deoxyribonucleic acid) of your sample was analyzed and we identified some 'mutations' or changes that are associated with this medical condition. Details regarding 'mutations' or changes detected in your DNA are given below:


rs1295686 IL13 5 A GG rs1342326 IL33 9 C AC

rs1588265 PDE4D - RPL31P8 5 G AG rs2244012 RAD50 5 G AG rs2284033 IL2RB 22 G AG rs3771166 IL18R1 2 G AG

rs7216389 GSDMB 17 A AA

rs744910 SMAD3 15 G AA

rs7922491 PRKG1 10 A GG

rs9273349 HLA-DQ region 6 G GG



the final outcome of the condition. Note: There could be other variants, not screened by this test.

Risk Factors In recent years, the increasing incidence of asthma is primarily due to urbanization and air pollution. Genetic factors may also determine the disease outcome. Asthmatic individuals are sensitive to various

“stimulants” that trigger the response such as pollen, dander, environmental tobacco smoke, animal hide or hair, chemical irritants, and pollutants. Generally, cold weathers of night or early morning and excessive physical activity aggravate the asthmatic response. Age: Asthma attacks people of all age groups. However, it is often an early onset disorder. The male gender is at a higher risk of incurring childhood asthma; however, the risk of adult asthma may be a little high in females. Generally, the disease manifests itself as allergy in children. Family history: The risk increases by at least 3-fold in individuals reported to have family history of asthma. Other conditions: The risk is also high in people who are hypersensitive to allergens. Clinical conditions such as atopy (eczema, allergic rhinitis) or airway hyper-reactivity may also lead to asthma or seasonal allergies. General risk factors: General risk factors include smoking and breathing allergens/stimulants. AGE RELATED MACULAR DEGENERATION



population

17 in 100 3 out of 3

Age-related macular degeneration is an irreversible condition and a major cause for vision loss in aging population across the world. This condition is usually seen in people over 50 years of age and the progression of the disease could be either very slow or very aggressive. With advancing age, macula of eyes is completely degenerated due to formation of drusen (cellular debris) between retinal pigment epithelium and choroid. Due to accumulation of drusen , eyes start losing blood supply, which results in the loss of nutrition required for proper functioning. There are two types of AMD known as dry AMD and wet AMD.

Nonexudative or dry AMD: The nonexudative type is a condition that includes soft and hard drusen and geographic atrophy. This condition progresses slowly and may take many years for the complete loss of vision.

Exudative or wet AMD: In neovascular or exudative type, the Bruch’s membrane of the eye is

damaged and the blood vessels grow into choroid. These blood vessels bleed, leading to leakage

of blood underneath macula and other lipid materials, thereby developing a dense scar covering

the entire macular region. This is a serious form of the disease that leads to blindness in a short

period. Genetics

Genetics has a greater impact on the risk of developing AMD. With a family history first-degree relative

with AMD, the risk to develop the disease increases by is 6.6 times. The chances of a sibling to

developAMD increase by 4.8 times to develop early form and the chances to develop late AMD increase

by 19.8 times, if one sibling is diagnosed with this disease. The genetic content, DNA (deoxyribonucleic

acid) of your sample was analyzed and we identified some 'mutations' or changes that are associated with

this medical condition. Details regarding 'mutations' or changes detected in your DNA are given below:

SNP ID Gene Chr. # Risk Allele Genotype rs10490924 ARMS2 10 A AC rs1329428 CFH 1 G GG rs429608 SKIV2L 6 G GG

Note: Genetic component of an individual form a minor fraction of the equation and are not the absolute causative factors that determine the outcome. There could be several other influential elements acting simultaneously that decide the final outcome of the condition. Note: There could be other variants, not screened by this test. Risk Factors Age & Gender: As it is implied from the name of the disease, older people aged above 60 years are at risk of developing AMD. Affecting of the vision though early onset of the disease, i.e., before 50 years of age, is also possible. The elderly aged group has a three-fold increased risk of developing the disease. Females are more likely to develop AMD than males. Genetics: The genes responsible have been reported and the inheritance of these genes has been studied. Having family history of AMD also increases chances of developing this disease. Smoking: Studies reveal that smoking can act as a lead for development of disease; with two- to three-fold increased risk compared with non-smokers, though the reasons are not clear. The reason can be attributed to the fact that smoking lowers the levels of antioxidants circulation in the body. Exposure to sunlight, alcohol consumption, and hypertension are also said to be the risk factors for the development of AMD, but research is still in progress on detailing how these factors are associated with AMD.

SKIN FRECKLES Freckles are small dark pigmented spots on top layer of the skin (keratinocytes), occurring as a result of exposure to sun rays. The spots are enriched with melanin pigment and are very prominent on lighter skin. Freckling is also referred to as melanism. Freckles are not associated with any sort of inflammatory disorders. Generally, any damage to melanocytes (cells that produce melanin pigment) lead to abnormal and uneven accumulation of melanin pigment in skin cells. Genetics Polymorphism in few skin pigmentation related genes such as TYR and MC1R have been reported for their correlation with developing freckles among individuals. Furthermore, SNPs found in other genes like IRF4 are reported to have significant association with freckling. Details regarding 'mutations' or changes detected in your DNA are given below:


TYR rs1042602 CC Low likelihood for skin /facial

freckling IRF4 rs12203592 GG

FANCA rs12931267 CC





Risk Factors

Intense exposure to UV rays emerging from sunlight, family history and genetic factors all determine an individual’s risk

of developing freckles.

HAIR MORPHOLOGY Hair morphology is genetically driven to a large extent. The thickness, shape and colour of hair widely vary across all ethnic groups and are controlled by several genetic variants. Genetics Trichohyalin gene (TCHH), expressed in hair follicles determine the curliness factor of hair, among individuals. Trichohyalin protein secreted by this gene is involved in cross linking of keratin filaments in hair. Variations in this gene partly account for hair being straight or wavy, in nature. Ancestral alleles of TCHH are reported to correlate with ancestral trait of curlier hair and alternative or derived alleles are associated with straight hair. The thickness factor is partly accountable by FGFR2 gene, particularly in Asians. Hair density is directly proportional to the number of hair follicles. Similarly, hair colour like that of blonde or black or red is determined by certain hair pigmentation related genes like OCA2 and MC1R. OCA2 gene functions to produce melanin pigment in the body. However, genetic segment in the near upstream region of OCA2, specifically in the HERC2 locus, are reported to regulate the expression of OCA2 gene. Thus increase or decrease in the expression of OCA2 gene is partly controlled by this stretch of genetic sequence. Hence polymorphic variants of HERC2 gene account for variation in hair pigmentation. Furthermore, red hair is largely accountable by MC1R gene. Hair Texture


TCHH

rs11803731

AA

Low likelihood for straight

hairs Note: Genetic component of an individual form a minor fraction of the equation and are not the absolute causative



Note: There could be other variants, not screened by this test. Loci Marker Genotype Inference

HERC2

rs12913832

AA

Likely to have darker shade

of hair colour (brown / dark

brown / black) compared to

lighter hair shade (blonde or

red) Note: Genetic component of an individual form a minor fraction of the equation and are not the absolute causative




TANNING Sun tan refers to darkening of skin that occurs after exposure to sunlight or UV rays. Tans are primarily due to skin darkening pigment – melanin, induced in the body as a result of UV exposure. The extent of tanning increases with intensity of UV rays and duration of its exposure. Sun tanning may lead to skin cancer in severe cases.

Genetics Polymorphism in few skin pigmentation related genes such as TYR, MC1R, HERC2 and MATP have been reported for their correlation with suntanning ability among individuals. Furthermore, SNPs found in other genes like IRF4 and GRM5 are reported to have significant association with suntan. Details regarding 'mutations' or changes detected in your DNA are given below:


TYR rs1126809 GG Slightly susceptible to tanning

IRF4 rs12203592 GG

HERC2 rs12913832 AA





Risk Factors Certain elements like lighter skin, family history of sunburns/skin blisters or skin cancer, intense UV exposure etc increase one’s lifetime risk of developing suntan. Apart from all above factors, genetic variants too play a major role in determining tanning ability. SKIN PIGMENTATION Skin pigmentation, or skin color, depends on melanin's density and distribution in the skin tissue (melanin index). Inter-individual variability is indirectly measured (quantified) through skin reflectance spectroscopy, which classifies skin type into low- (L) and high-reflectance (H) groups. Genetics The genetic basis of skin pigmentation has been extensively studied in Caucasian, African and Asian studies. Findings report that allelic variation in the TYR (tyrosinase enzyme) and the SLC45A2, SLC24A5 genes (solute carrier family of proteins), affect skin reflectance in South Asians. These loci have also been implicated in other skin-associated conditions such as vitiligo, albinism and melanoma. The SLC24A5 gene is highly expressed in melanocytes, and multiple studies conducted in Indian subjects have highlighted its association with geographic variation in skin color of different ethnicities. Details regarding 'mutations' or changes detected in your DNA are given below:


TYR rs1042602 CC Slightly high likelihood for

lighter skin SLC24A5 rs1426654 GG





Risk Factors Melanin: One of the primary pigments found in our skin, melanin is a key determinant of skin color. Latitude/UV irradiation: Natural selection causes people in high-UV areas to have darker skin, and vice versa.

SUNBURNS Injury caused on skin due to intense exposure to sunlight. The ultraviolet radiations emerging from sunrays cause excessive damage on skin. Sunburns may generally manifest as hot red regions/spots on skin (erythema) and may lead to skin blisters or even skin tumor under severe conditions. Sunburns are often painful and may take several days to subside. Genetics SNPs observed in NTM, MC1R and IRF4 genes are found to be significantly associated with increased number of sunburns. NTM is a member of the IgLON family of cell adhesion molecules. The gene is actively involved in skin aging process. The SNP rs12421680 on NTM gene is associated with increased number of sunburns and higher risk of melanoma. Similarly SNPs on two pigmentation related genes MC1R and IRF4 are found to have significant association with increased number of sunburns. Details regarding 'mutations' or changes detected in your DNA are given below:


NTM rs12421680 GG Low likelihood for sunburns

IRF4 rs12203592 GG





Risk Factors Light and/or unprotected skin, intense exposure to sunrays, use of photosensitizing medication are few risk factors associated with sunburns.

INHERITED CONDITIONS G6PD DEFICIENCY Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked recessive condition prevalent across the globe with nearly 400 million people affected. The enzyme deficiency can be either acquired over one’s lifetime or inherited from parents. However, affected people are largely asymptomatic unless triggered externally by certain synthetic drugs, fava beans or infections. Complications The enzyme deficiency leads to chronic haemolytic anaemia (significant reduction in haemoglobin levels) on intake of certain drugs that induce oxidative stress in blood cells. Several anti-malarial drugs such as primaquine or dapsone can trigger haemolytic anaemia in G6PD deficient people. In neonates, excessive haemolysis or anaemia leads to significant rise in bilirubin levels causing jaundice. Chronic nonspherocytic haemolytic anaemia and favism are other adverse physiological effects associated with G6PD enzyme deficiency. However, it should also be noted that the enzyme G6PD is required for malarial parasite to grow and multiply on RBCs. Enzyme deficiency may partially impair the growth of malarial parasites thereby conferring higher resistance to malaria in comparison with G6PD positive population. Genetic significance The housekeeping gene G6PD is located in X-chromosome and is around 18kb long. Many missense mutations that are clinically pathogenic have been reported to be associated with the gene. Most of these variants affect the enzyme either structurally or functionally, leading to clinical complications in individuals. The gene sought the attention of World Health Organization in correlation with G6PD deficiency and health risks associated with it. The two widely reported non-synonymous point mutations affecting G6PD enzyme deficiency are val68met and Asn126Asp commonly referred with mutation ID rs1050828 and rs1050829 respectively. The variants are associated with adverse drug toxicity for several antimalarial drugs such as amodiaquine, artesunate, chlorproguanil, sulfadoxine, dapsone and primaquine. Nucleotide position 563C->T variation in exon 6 of the gene is yet another non-synonymous mutation substituting for amino acid serine to phenylalanine at position 188 of the enzyme affecting its stability. This is typically referred to as the “Mediterranean variant” with mutation ID rs5030868. This variant is commonly associated with G6PD enzyme deficiency in India, accounting for nearly 60.4% of cases particularly in the urban sectors of the country. Certain other markers popularly known as 'G6PD-Kerala-Kalyan' (Glu317Lys), 'G6PD-Orissa' (ala44gly) and 'G6PD Namoru' (Tyr70His ) are exclusively associated with the condition among Indian population. Genetic testing of G6PD locus is necessary for determining the carrier status of individuals and thereafter adopt suitable precautionary measures as suggested by genetic counselors. Your Profile for G6PD Deficiency


G6PD

rs1050828 GG You do not have variants for G6PD enzyme

deficiency and hence may not be at risk for

hemolytic anaemia when exposed to certain

medications or food groups

rs1050829 AA

rs5030868 GG

rs78478128 GG

Note: There may be other markers/variants of G6PD deficiency that are not screened here. Note: G6PD deficiency is an X-linked recessive disorder and males have only one ‘X’ chromosome which comes from the mother. Hence if the mother carries homozygous variants for G6PD deficiency, the male offspring will certainly develop the condition. However, the female offspring has two ‘X’ chromosomes and has to inherit 2 variant copies of the gene (from both parents) in order to have G6PD deficiency. Treatment Avoiding exposure to triggering factors (drugs and food groups including legumes - beans, peas and lentils) can reduce the disease severity in adults. Neonatal screening for G6PD deficiency is necessary to avoid health complications often observed in newborns (anaemia associated with jaundice). PHENYLKETONURIA Phenylketonuria (PKU) is a rare genetic disorder in which the metabolism of amino acid phenyl alanine is affected. It is an autosomal recessive abnormality as it manifests only if both the parents are carriers of mutant alleles. Hence the risk for PKU may be high in consanguine marriages. Phenylketonuria is characterized by faulty secretion or deficiency in the activity of the enzyme Phenyl Alanine Hydroxylase (PAH), which catalyses the metabolic conversion of phenyl alanine to amino acid tyrosine, in the liver. As a result, there is excessive accumulation of phenyl alanine in the body leading to cytotoxicity. Increased phenyl alanine concentration in the body is detected in urine and hence the term Phenylketonuria. Complications The extent of PAH deficiency may lead to wide spectrum of disease severity ranging from non-PKU hyperphenylalaninemia to mild phenylketonuria and the most severe form, classic phenylketonuria. Classic phenylketonuria may manifest itself into several acquired health complications that are severe and irreversible. Impaired cognitive development leading to mental disorders like hyperactivity, irritability and Attention Deficit Disorder ADD are some common symptoms of PKU. Associated mental disorders are often because of neurotoxic effects of unmetabolized phenyl alanine excessively accumulating in the body and reaching the brain. Epileptic seizures are also reported in some cases. The enzyme deficiency results in reduction of tyrosine concentration in the body. This leads to pigmentation problems of skin and hair as tyrosine is directly involved melanin production. Hence, light skin with skin lesions and blonde hair is reported in cases of severe PKU. Genetics The PAH gene has 13 exons. Hundreds of mutations are studied and reported within exons and their flanking sequences. Most of these mutations are pathogenic and lead to inefficient enzyme activity. However, some mutations may not trigger severe form of classic phenylketonuria. Missense mutation constitutes nearly 60% of overall reported variations. Deletion, splice type and non-sense mutations account for nearly 28% of variations globally. Few silent mutations are also observed. Large number of sequence variations particularly in exon 6 and exon 7 region of PAH are reported. The p.R408W (missense mutation - exon 12), IVS10-11G>A (splice site mutation - intron 10) p.I65T (missense mutation - exon 3) and p.R261Q (missense mutation - exon 7) are widely reported variants of PAH found to have greater association with PKU. Few variants are reported from Indian race and are mostly observed in exon 7 region of the gene. Genetic testing of phenylalanine hydroxylase locus is necessary for determining carrier status of individuals and thereafter adopting precautionary measures suggested by genetic counselor, in order to have healthy offspring. Therefore the test is recommended for 'at-risk' families.

Your Profile for Phenylketonuria


PAH

rs5030843 GG

You do not have variants for

Phenylketonuria. Hence you may not

be a carrier for disease phenotype -

Phenylketonuria

rs5030849 GG

rs5030853 CC

rs5030857 GG

rs5030858 GG

rs5030860 AA

rs5030861 GG

rs62642933 AA

Note: There may be other markers/variants not screened here.

Note: If both the parents are carriers of PKU variants, then there is 25% probability of the child being born with PKU.

However, there is 50% probability of the child being born as a carrier for PKU. Chance of having normal child (not even

a carrier) is 25%.

Treatment Treatment generally involves lifetime modification in diet pattern. Subjects are recommended a low protein diet, particularly low in phenyl alanine content and are constantly monitored by dieticians or physicians. Since food is the only source of phenyl alanine in the body, adhering to appropriate diet may alleviate the effects of PKU. Neonatal screening for PKU is a mandatory procedure where infants undergo testing as a preventive measure and if positive are treated young. DRUG RESPONSES 5 - FLUOROURACIL (5-FU) Brand name Adrucil® Prescribed as An anticancer drug for treatment of different cancers. Risks Genetically unfavorable condition may trigger drug toxicity in patients taking the therapy. Your response to 5-fluorouracil Marker identified in your genome and its correlation with response to 5-fluorouracil:


DPYD

rs3918290

GG

Low risk for drug

induced toxicity. Note: This test looks for the most common and already-proven genetic variants associated with the therapy and does

not screen for rare markers affecting the drug response.

Your genotype description You have 2 copies of regular base ‘G’ on your gene DPYD, chromosome 1 and position '97915614'. Genetic interpretation

This indicates that you may not be genetically susceptible for drug induced toxicity and you may be given the regular therapy. However, your physician shall decide on the drug and the dose depending on other clinical factors or medications you might be taking. Drug information 5-Fluorouracil is an anti-cancer drug, which is recommended to treat different types of cancers. It has been in use for the last two decades. Some of the cancers targeted by the drug are colon, breast, rectum, head and neck and ovary. It is an antimetabolite, structurally an analog of uracil. It interferes with RNA processing and DNA synthesis of cancerous tissue, thereby impeding the growth and metastasis of cancer cells. Adverse effects The drug exerts several adverse effects in susceptible patients. However, response to the drug largely varies from one individual to another. Majorly associated side effects include grade 3 to 4 toxicity like depletion of WBCs, (triggering microbial infections) and RBCs (leading to anemia). Mouth sores, nausea, vomiting, diarrhea, inflammation of GIT track, skin rashes or hand-foot syndrome are other symptoms associated with drug toxicity. Genetic significance Genetic elements largely determine the response of patients to the drug. People with specific genetic variation may not be able to metabolize the drug efficiently. This may lead to drug accumulation and toxicity. Dihydropyrimidine dehydrogenase (DPYD) is actively involved in breaking down 5FU. The catabolic enzyme acts upon the drug and processes it further to cytotoxic nucleotides, capable of inhibiting thymidylate synthase, which is actively involved in cell proliferation. Variants of DPYD gene produce a faulty enzyme incapable of transforming the drug to its active moiety. Hence, the drug accumulates in the body leading to increased toxicity. ABACAVIR Brand name ZIAGEN® Prescribed as An antiviral drug given in combination with other antiretroviral drugs for the treatment of human immunodeficiency viral (HIV) infection. Risks Genetically unfavorable condition may trigger an adverse drug toxicity (hypersensitive reaction) in patients taking the drug. Your response to abacavir Marker identified in your genome and its correlation with response to abacavir:


HLA-B*5701

rs2395029

AA

Low risk for drug

induced toxicity. Note: This test looks for the most common and already-proven genetic variants associated with the therapy and does not screen for rare markers affecting the drug response. Your genotype description

You have 2 copies of regular base ‘A’ on your gene HCP5, chromosome 6, position ‘31431780’, inferring that you are most probably HLA-B*5701 negative. Genetic interpretation This indicates that you may not be genetically susceptible for developing drug induced toxicity and you may be given the regular therapy. However, your physician shall decide on the drug and the dose depending on other clinical factors or medications you might be taking. Drug information Abacavir is recommended to HIV-1 infected patients to fight against AIDS or AIDS related illness. The drug is a synthetic nucleoside and is phosphorylated to form an analog of guanine. It inhibits the viral DNA synthesis and thereby combats the viral replication in human body. Abacavir is generally prescribed in combination with other drugs to treat HIV. Practicing safe sex and good life style are beneficial in fighting against HIV. Adverse effects The drug by large is safe. However, in some people it may trigger severe Hyper Sensitive Reaction (HSR), which is a multi-organ syndrome, characterized by fever, rashes on skin, headache, nausea, cough, sore throat, vomiting, diarrhea, breathing difficulties and abdominal pain. Gastrointestinal symptoms are reported in significant number of cases. Lactic acidosis in blood and abnormalities in liver and kidney are also reported. Genetic significance Genetic factor of an individual significantly determines the drug response. HLA-B gene that encodes for the heavy chain of MHC class-1 molecule plays a crucial role in presenting the antigenic peptides to the body's immune system. Variation in gene sequence of HLA-B triggers severe HSR in the mutants (HLA-B*5701) of the gene. Southwest Asians, particularly Indians have the highest prevalence rate of HLA-B*5701 of up to 20% of population, whereas Africans have the least prevalence rate. Up to 8% of patients taking abacavir experience hypersensitive reaction if genetic pre- screening is not performed. It is important to understand that HIV infection by itself triggers a wide range of symptoms and additionally the patient may be prescribed a combination therapy involving multiple drugs. Hence, the root cause of HSR may be obscured. Therefore, genetic pre-screening of HLA-B*5701 variant is recommended by the United States Food and Drug Administration (FDA) before starting or re-starting the drug therapy in patients. This involves identifying the corresponding tag marker for HLA-B*5701 variant, i.e., 'rs2395029 of HCP5'. ASPIRIN Brand name Ecotrin® Prescribed as An analgesic, antipyretic, anti-inflammatory or antiplatelet agent. Benefits Aspirin therapy can contribute to significant reduction in cardiovascular disease (CVD) among genetically favorable individuals. Your response to aspirin Marker identified in your genome and its correlation with response to aspirin:


LPA

rs3798220

AA

No significant risk

reduction of CVD with

Aspirin therapy. Note: This test looks for the most common and already-proven genetic variants associated with the therapy and does


Your genotype description This indicates that you may not be genetically prone to respond better to Aspirin therapy (when prescribed for CVD). However, your physician shall decide on the right drug and dose depending on several clinical factors or medications you might be taking. Genetic interpretation You have 2 copies of 'A' allele on your gene LPA, chromosome 6 and position 160540105. Drug information Aspirin is a salicylate drug. It has analgesic, antipyretic, anti-inflammatory and antiplatelet properties. Most often it is prescribed to reduce fever and alleviate pain or inflammation in the body. Sometimes it is used to treat cardiovascular diseases (mainly heart attack or stroke) caused from platelet aggregation. Apart from above mentioned pathological conditions, aspirin is given to treat many more disorders including certain cancers. Adverse effects Although serious side effects are rare, mild adverse events such as headache , indigestion, bleeding and allergic reactions are reported. Genetic significance LPA gene encodes a serine proteinase whose elevated plasma level results in atherosclerosis thereby leading to increased CVD risk. People with minor allele ‘G’ at rs3798220 of LPA gene are at two fold higher risk of incurring cardiovascular disease. However, they seem to respond faster and better or benefit more from aspirin therapy than non-carriers of ‘G’ allele. They show a relative CVD risk reduction of 56% upon medication. This is primarily because the altered protease-like domain of the encoded protein is better treatable by the therapy. The NNT (Numbers Needed to Treat) factor was reduced significantly for carriers of minor variant - ‘G’ on aspirin therapy. CLOPIDOGREL Brand name Plavix® Prescribed as An anti-platelet drug, inhibiting platelet aggregation and preventing blood clot formation in the body. Risks Under genetically unfavorable conditions, the drug therapy could be less effective leading to reduced inhibition of platelet aggregation. Your response to clopidogrel Marker identified in your genome and its correlation with response to clopidogrel:

Loci Genotype Inference

CYP2C19, ABCB1, PON1, P2RY1

AA_AA_GG_AG_GG_*1/*2

Intermediate metabolizer.

Reduced drug absorption.

Therapy inefficient.

Note: The current version of This test does not look for rs28399504 marker associated with the therapy.

Your genotype description You have 1 base variation of ‘G to A’ on your gene CYP2C19, chromosome10, position ‘96541616’ (referred as rs4244285);You have 2 base variations of ‘G to A’ on your gene ABCBC1, chromosome 7, position ‘87138645’ (referred as rs1045642);You have 2 copies of regular base ‘A' onyour gene PON1, chromosome 7, position ‘94937446’ (referred as rs662);You have 2 base variations of ‘A to G’ on your gene P2RY1, chromosome 3, position ‘152554357 ’ (referred as rs701265). Genetic interpretation According to your genotypes, this drug might not be activated and therapy could be ineffective. Hence you may be given an alternate therapy. However, your physician shall decide on the drug and the dose depending on other clinical factors or medications you might be taking. Drug information Clopidogrel is an anti-platelet drug that inhibits platelet aggregation and thereby prevents blood clot formation in the body. It hinders narrowing of blood vessels and maintains easy flow of blood in the body. It decreases the risk of heart disorders and strokes primarily in patients who have incurred a cardiovascular attack. Adverse effects Fatal adverse effects from the therapy are very rare. Most frequent mild reactions include nausea, diarrhea, fever, bleeding or bruising and skin rashes. Occasional side effects may include bleeding in stomach and brain or variations in blood pressure levels. Major adverse cardiovascular events and high risks of stent thrombosis are reported as few rare life threatening events associated with the therapy. Genetic significance Genetic factors significantly determine response of the patient to the drug. Clopidogrel undergoes 'bioactivation' within the body, to form an active metabolite which interacts with blood platelets. Several enzymes are involved in this transformation. Variation in genetic sequence of these enzymes affects the enzyme function.This alters pharmacokinetics of the drug, leading to ineffective response in some people or can even lead to major adverse cardiovascular events. The hepatic CYP2C19 is one such enzyme involved inbioactivation of the drug. Several variants of CYP2C19genetic sequence have been reported to correlate with drug efficacy in patients. Some variants impair the functional domain of the enzyme thereby inhibiting the interaction with platelets. On the other hand, variants reported in the regulatory region of the gene are known to enhance the function of the enzyme. Furthermore there are Indian specific polymorphic regions at ABCB1, PON1 and P2RY1 affecting the drug response. Variants in these regions affect drug absorption and activation, thereby playing a crucial role in inhibition of platelet aggregation. FLUCLOXACILLIN Brand name Floxapen® Prescribed as

An antibiotic drug for treating bacterial infections. Risks Under genetically unfavorable condition, prolonged treatment may trigger an adverse drug reaction of liver toxicity. Your response to flucloxacillin Marker identified in your genome and its correlation with response to flucloxacillin:


HLA-B*5701

rs2395029

AA

Low risk for drug induced liver

toxicity. Note: This test looks for the most common and already-proven genetic variants associated with the therapy

and does not screen for rare markers affecting the drug response.

Your genotype description You do not have risk allele in the tag marker, inferring that you may be HLA-B*5701 negative. Genetic interpretation This indicates that you may not be genetically susceptible to develop drug induced toxicity and you may be given the regular therapy. However, your physician shall decide on the drug and the dose depending on other clinical factors or medications you might be taking. Drug information Flucloxacillin is a penicillin class antibiotic commonly preferred to fight staphylococcal and other gram positive bacterial infections (streptococci, pneumococci). It is also effective against some strains of gram negative aerobic or anaerobic bacteria. It is generally prescribed to treat bacterial infections of the skin, urinary tract, respiratory tract, enteritis and other tissues. Adverse effects Stomach ache and diarrhoea are commonly reported mild reversible side effects. Uncommon effects could be skin rashes, jaundice and bruising of mucous membranes. Occasional cases of severe liver damage is associated with prolonged or repeated course of treatment. This may lead to notable yellowing of skin and eyes. Genetic significance Genes involved in the metabolism of the drug in connection to its adverse reaction are not well known. However, MHC loci may share a crucial role in determining the drug response of an individual. Several genes like TNF, HSPA1L, HLA and ST6GAL1 may correlate with drug induced liver injury. The MHC loci HLA-B*5701 has a greater significance of association with drug toxicity. HLA-B*5701 is commonly detected by screening for its tag marker ‘rs2395029’. One out of 500–1000 people with HLA-B*5701 marker may have liver toxicity when treated with the drug. However, cases of liver toxicity with HLA-B*5701 are hardly seen in Asian countries. METFORMIN Brand name Glucophage® Prescribed as An anti-diabetic drug, to control blood sugar levels in type -2 diabetic patients. Benefits

Genetically favorable conditions may increase the chance of positive drug response. Your response to metformin Marker identified in your genome and its correlation with response to metformin:


ATM

rs4585

CC

High likelihood for positive drug

response. Note: This test looks for the most common and already-proven genetic variants associated with the therapy and does


Your genotype description You have 2 'C' alleles on your gene ATM, chromosome 11, position 108239628 (referred as rs4585). Genetic interpretation This indicates that your genetic inclination of having an effective response for the drug therapy may be high. However, your physician shall decide on the drug and the dose depending on other clinical factors or medications you might be taking. Drug information This is a well known anti-diabetic drug, used to control blood sugar levels in human body and is prescribed to treat type-2-diabetes in adults and children. It acts by several means like increasing insulin sensitivity, decreasing glucose secretion in liver (termed as ‘gluconeogenesis’), increasing peripheral uptake of glucose and reducing gastrointestinal absorption of glucose. It activates the enzyme 'AMP-activated protein kinase' in the liver, which plays a crucial role in suppressing gluconeogenesis. Adverse effects General side effects include nausea, diarrhea, headache, indigestion, difficulty in breathing, fever and weight loss. Most of these side effects are reversible and mild. Lactic acidosis (increased production of lactic acid in the blood stream) is reported in rare cases of metformin toxicity. Genetic significance Several genetic markers are reported to determine response to metformin. The drug response varies widely from person to person. People with specific markers seem to inherit a good chance of positive response to the therapy. ATM (Ataxia Telangiectasia Mutated)is one such gene correlated with better drug response. The gene encodes for a 370kda protein, which functions as a cell cycle checkpoint kinase. It activates many other proteins involved in signaling pathways. One of the target protein AMPK (AMP-activated protein kinase ) is directly involved in the activation of metformin. Hence, variation in ATM gene sequence, has an indirect effect on the drug therapy. SIMVASTATIN Brand name ZOCOR® Prescribed as A lipid lowering drug recommended for prevention of coronary heart disease. Risks

Under genetically unfavorable condition, the drug may trigger an adverse reaction of myopathy (muscle toxicity) or rhabdomyolysis (degeneration of muscles with acute kidney injury) in patients taking the therapy. Your response to simvastatin Marker identified in your genome and its correlation with response to simvastatin:


SLCO1B1

rs4149056

AA

Low risk for drug induced

toxicity. Note: This test looks for the most common and already-proven genetic variants associated with the therapy and does not screen for rare markers affecting the drug response. Your genotype description You have 2 copies of regular base ‘A’ on your gene SLCO1B1, Chromosome 12 and position 21331549 (referred as rs4149056). Genetic interpretation This indicates that you may not be genetically susceptible for developing drug induced toxicity and you may be given the regular therapy. However, your physician shall decide on the drug and the dose depending on other clinical factors or medications you might be taking. Drug information Statins are lipid lowering drugs recommended for the prevention of primary and secondary cardiovascular disease. Concomitant administration of the drug along with regular diet and exercise have found to reduce levels of LDL cholesterol (Low Density Lipoprotein) or bad cholesterol and also increase the level of HDL cholesterol (High Density Lipoprotein) or good cholesterol in the body. Adverse effects Statins have wide therapeutic index and are safe in general. Some of these adverse reactions could be non-serious and reversible, while rare cases could also be fatal. Most common adverse effects include muscle toxicity or 'myopathy' and rare cases of rhabdomyolysis (degeneration of muscles with acute kidney injury). Genetic significance Genetic elements significantly determine the response of patients to the drug. People with specific marker in their genotype are unable to metabolize the drug efficiently. Hence, the drug is accumulated in the muscles leading to muscle toxicity or 'myopathy'. SLCO1B1 gene encodes the protein OATP1B1, which is associated with hepatic uptake of the drug. Variation in gene sequence of SLCO1B1 impairs the normal function of the encoded protein, altering the plasma concentration of statins and increasing related muscle damage. THIOPURINES Brand name Purinethol® Prescribed as A chemotherapeutic drug in treatment of cancers or as immunosuppressant drug in treating autoimmune disorders. Risks

Under genetically unfavorable conditions, the therapy leads to bone marrow suppression and causes drug toxicity. Your response to thiopurines Marker identified in your genome and its correlation with response to thiopurines:


TPMT

*1/*1

High enzyme activity. Low risk for drug induced toxicity.

Note: This test looks for the most common and already-proven genetic variants associated with the therapy and does not screen for rare markers affecting the drug response. Your genotype description You have 2 copies of regular base 'G' on your gene TPMT, chromosome 6, position '18143955' (referred as rs1800462); You have 2 copies of regular base 'G' on your gene TPMT, chromosome 6, position '18139228' (referred as rs1800460); You have 2 copies of regular base 'A' on your gene TPMT, chromosome 6, position '18130918' (referred as rs1142345). Genetic interpretation This indicates that you may not be genetically susceptible to drug toxicity. Hence the therapy may be recommended for you. However, your physician shall decide on the drug and the dose depending on other clinical factors or medications you might be taking. Drug information They are a class of cytotoxic drugs prescribed to treat several health conditions. They function as antimetabolites for cancers (leukemia, lymphoma) and immunosuppressants for auto immune diseases (rheumatoid arthritis) or inflammatory diseases (Crohn's disease, ulcerative colitis). They are also widely used in transplantation medicine (kidney). Biochemically the drug is a purine analog and is more reactive than regular purine bases. It is incorporated into DNA and /or RNA causing strand breaks and cross-links. Azathioprine, 6- mercatopurine, 6-thioguanine are examples of thiopurine drugs. Adverse effects The adverse reactions of the therapy and its severity may vary from person to person. Some common and mild side effects include nausea, vomiting, diarrhea, skin reactions, hair loss, loss of appetite, flu-like symptoms, fever, and chills. Occasional life threatening adverse events are reported in susceptible patients. Drug induced hepatotoxicity (liver toxicity) and myelosuppression (bone marrow suppression) are few of the kind observed and reported. Bone marrow suppression leads to significantly decreased count of blood cells. This causes anaemia and weakens immunity in patients further, triggering several other infectious diseases. Genetic significance Thiopurines are administered as pro-drugs and further require biological activation to exert cytotoxic action. Azathioprine is reduced to 6MP, non-enzymatically. Both 6MP and 6TG are sequentially metabolized to form the final active cytotoxic compound ThioGuanine Nucleotide (TGN). Several enzymes catalyze the process. The cytotoxic TGN then is incorporated into DNA and /or RNA, causing strand breaks and strand crosslinks, destroying cancer cells. However, excess cytotoxic activity of the drug is regulated by the

enzyme Thiopurine S-MethylTransferase (TPMT). The enzyme catalyzes deactivation of the drug through S- methylation reaction. Genetic variations of TPMT loci drastically affect the enzyme activity. As a result, the drug is poorly metabolized. If given the normal dose of drug in such people, it leads to enhanced cytotoxicity due to accumulation of unmetabolized drug in the body. TPMT deficiency is an autosomal recessive trait and primarily determines inter-individual differences in drug response. Its association with drug toxicity has gained notable significance. Like many other new therapeutic drugs, prolonged treatment course of thiopurines is associated with

drug induced liver injury (Hepatotoxicity). Furthermore, the drug causes characteristic myelosuppression

in TPMT deficient people. There are occasional cases of serious and fatal myelosuppression caused by the

drug.

Around 1% of population has the drug susceptible homozygous risk genotype and around 7% of people

inherit the heterozygous genotype. Rest of the fraction constitutes normal wild type gene.

WARFARIN Brand name COUMADIN® Prescribed as An anticoagulant drug to treat heart attack and stroke. Risks Genetically unfavorable condition may trigger resistance or may increase sensitivity to the drug. This may lead to increased risk of thromboembolism or bleeding in patients taking the therapy. Your response to warfarin Marker identified in your genome and its correlation with response to warfarin:


CYP2C9 CYP2C9*1/*1 Low risk for drug sensitivity.

*Note :The current version of This test does not look for VKORC1 marker associated with the therapy. Your genotype description You have 2 copies of regular base ‘A’ on your gene CYP2C9, chromosome 10 and position '96741053' (referred as rs1057910); you have 2 copies of regular base ‘G’ on your gene CYP2C9, chromosome 10 and position '96702047'(referred as rs1799853). Genetic interpretation This indicates that you may not be genetically sensitive for the drug therapy and you may be given the regular warfarin dose. However, your physician shall decide on the drug and the dose depending on other clinical factors or medications you might be taking. Drug information Warfarin is the most widely recommended anticoagulant (blood thinner) used to treat thrombotic disorders (formation of 'thrombus' or blood clot in blood vessel). It inhibits the formation of clotting factors thus reducing blood clots in arteries and veins, of the body. It is generally prescribed in conditions of arrhythmia, myocardial infarction and stroke.

Adverse effects The medication is safe in general; adverse events are reported occasionally. Most common side effects include nausea, vomiting, diarrhea, fatigue, loss of appetite, skin rashes, wheezing and difficulty in breathing, and abdominal pain. Medical cases of fatal bleeding or bruising are reported. Blood in urine and stool, nosebleeds and bleeding gums are associated with overdose of the drug. Genetic significance Genetic factors constitute a primary component that determine the optimal dosage of warfarin therapy. Liver condition and drug-drug interaction are very crucial factors in deciding the dosage along with other preliminary factors like age, sex and race of an individual. CYP2C9 and CYP4F2 enzymes catalyze warfarin drug metabolism in the liver. Variation in gene sequence of the two enzymes impairs the enzyme function. Hence, the regular drug metabolism is hampered. VKORC1 protein, the target molecule for warfarin, is associated with the conversion of vitamin K–epoxide to vitamin K. Variation in regulatory region of VKORC1 significantly lowers the protein production, thereby affecting the regular pharmacodynamics of the drug.

CONDITIONS COVERED Traits

TRAITS DESCRIPTION Adiponectin

Levels

Adiponectin is an adipocyte (fat cell) derived plasma protein, also known as the

'starvation hormone'. It modulates a number of metabolic processes, including

glucose regulation and fatty acid oxidation.

Age at

Menarche

Menarche is defined as the onset of menstrual cycle (menses) in females. A major

milestone in pubertal development, menarche is the beginning of the reproductive

lifespan of a woman.

Alcoholism

Alcoholism or alcohol dependence is a chronic, progressive disease where victims

become “addicted” to alcohol and face severe repercussions while trying to give up.

Alcohol Flush

Reaction

Alcohol flush reaction is a condition where people experience flushes or blotches on

the face and body when they consume alcohol. Blood Pressure

Normal blood pressure should be less than 120/80 mmHg. Blood pressure higher

than normal is called hypertension (high BP), and high BP is said to be present if it is

persistently at or above 140/90 mmHg. Body Mass

Index/Obesity

Body mass is measured using Body Mass Index (BMI), which is the best estimate of

a person's body fat based on individuals weight and height. Body mass index is

defined as the individual's body mass divided by the square of his or her height and

expressed in units kg/m2. Bone Mineral

Density

Bone mineral density (BMD) or bone density measures how much calcium and other

types of minerals are in an area of bone. BMD is used as an indicator of

osteoporosis and predicts the risk of bone fracture.

Caffeine

Consumption

The frequency of caffeine conumption, number of cups per day and/or units

consumed varies across all ages. This is explained by differing caffeine sensitivity

and metabolic response, due to genetic factors (apart from environmental influences

and social habits).

Cholesterol

Levels - HDL &

lLDL

Two kinds of lipoproteins carry cholesterol throughout our body, low-density

lipoproteins (LDL) and high-density lipoproteins (HDL). Having healthy levels of both

types of lipoproteins is important. High blood cholesterol is a condition in which one

has too much cholesterol in blood.

Diet Pattern

Genetic factors play an important role in influencing hunger pangs, satiety after

meals, metabolic rate and calorie requirements. This explains the predisposition of

certain individuals to be leaner (or) overweight, even if they are on the same diet.

Eye Colour

Eye colour technically refers to colour of iris (flat, circular structure) of the eye.

Pigments within iris largely determine the eye colour.

Homocysteine

Levels

Homocysteine is an amino acid of cysteine homologue produced primarily from

methionine. Methionine undergoes a terminal methyl transfer reaction to form

Homocysteine molecule. Ideally, optimal homocysteine levels are close to 7-8 μmol/

L.

Nicotine

Dependence

The addictive nature of nicotine (chief constituent in tobacco) makes smoking a

recurrent habit in both men and women.

Premature Premature or early menopause occurs within 45 years of age. Premature ovary

Menopause failures could either occur naturally due to genetic factors or be induced surgically

due to severe health complications.

PSA Levels

The level of PSA in blood of a normal person is very low. But the levels of this

antigen is known to be elevated in men with prostate cancer prostatitis

(inflammation of the prostate) and benign prostatic hyperplasia (enlargement of the

prostate) and urinary tract infections.

Triglyceride

Levels

Triglycerides are fat molecules in the bloodstream that provide energy to various

parts of the body. Triglycerides are produced by the body and obtained from diet.

Sports &

Fitness

Determines the muscle power-to-endurance in individuals.

Skin

TRAITS DESCRIPTION Freckles

Freckles are small dark pigmented spots on top layer of the skin, occurring as a

result of exposure to sun rays. Skin

Pigmentation

Skin pigmentation, or skin color, depends on melanin's density and distribution in the

skin tissue (melanin index).

Sunburns Injury caused on skin due to intense exposure to sunlight. Tanning Sun tan refers to darkening of skin that occurs after exposure to sunlight or UV rays. Diseases

Diseases DESCRIPTION Age Related

Macular

Degeneration

Age-related macular degeneration is a condition that causes irreversible loss of

vision in affected persons. This disease affects people above 50 years, and so is the

name. It is also a major cause for sight loss in aging population worldwide.

Alzheimer’s

Disease

Alzheimer’s disease is the most common form of dementia. It is irreversible,

degenerative, and progressive in nature. It affects memory, thinking, and behavior.

Amyotrophic

Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder that ends in

death within 3-5 years of onset in an individual. This condition is referred to as Lou

Gehrig's syndrome, after the New York baseball player afflicted with ALS.

Ankylosing

Spondylitis

Ankylosing spondylitis (AS) is a type of arthritis that primarily affects spine, although

it can affect other parts like shoulders, hips, ribs, heels, hands, feet, eyes and

intestine. Asthma

Asthma is a chronic inflammatory disorder of the airways, which causes attacks of

wheezing, shortness of breath, chest tightness, and coughing.

Atopic

Dermatitis

Atopic dermatitis (AD) is a type of eczema, which is a long lasting itchy inflammation

of skin. In most of the cases it may be accompanied by asthma or hay fever. Atrial

Fibrillation

It is an irregularity of the heart, typified by rapid heartbeat. It results in palpitation or

fibrillation of the two upper chambers of the heart – known as ‘atria’. Atrial

fibrillation is caused due to abnormal electric charges produced in the heart.

Basal Cell

Carcinoma

Basal cell carcinoma is a type of skin cancer that arises from deep basal cells of skin

layer. It is non-melanocytic and is common in Western countries.

Biliary Cirrhosis

Primary biliary cirrhosis is a rare autoimmune liver disease characterized by self

destruction of intrahepatic bile ducts causing cholestasis. It eventually results in

fibrosis and scarring of liver tissue (cirrhosis), due to decreased bile secretion and

toxin retention.

Bipolar

Disorder

Bipolar disorder, or manic-depressive illness, is a psychiatric condition resulting in

recurrent extreme mood swings. Clinically, these mood swings are categorized as

manic episodes and depressive episodes.

Bladder Cancer

Bladder cancer is a common urological neoplastic condition that affects both men

and women. It is known to be slightly more common among men than women.

Breast Cancer

Breast cancer is a type of cancer that affects the breast tissue, and is the most

common cancer in women. It is also the main cause of death from cancer among

women worldwide.

Cardiovascular

Disease

Cardiovascular disease is an umbrella term for many disorders that affect the normal

functioning of a heart.

Celiac Disease

Celiac disease (CD) is an autoimmune disorder wherein chronic inflammatory

reactions in the intestine are triggered by gluten, a constituent of wheat and related

grains (rye, barley, etc.). It is manifested by gluten intolerance in the body. Across the

globe, it is most prevalent in the West, where gluten is predominantly consumed

(bread/pasta/wheat-based products).

Chronic Kidney

Disease

Chronic Kidney Disease (CKD) is a progressive and irreversible renal condition

wherein the estimated glomerular filtration rate (eGFR) declines (<60 ml/minute is the

diagnostic criteria) resulting in increased proteinuria and/or albuminuria.

Chronic

lymphocytic

leukemia

Chronic lymphocytic leukemia is a cancer that affects bone marrow and blood. It

specifically originates from lymphocytes of bone marrow.

Colorectal

Cancer

Colorectal cancer or colon cancer originates from colon or rectum of gastrointestinal

tract. The early forms of tumors on the walls of colon or rectum are benign and are

called polyps, which later develop into malignant tumors causing colorectal cancer.

Coronary Heart

Disease

Coronary heart disease happens when the supply of blood and oxygen to heart cells

is reduced due to narrowing of blood vessels (coronary arteries) that innervate the

heart. This is caused by 'plaques' found in the walls of the arteries, carrying blood to

the heart.

Crohn's Disease

Crohn’s disease or regional enteritis is an inflammatory bowel disease that can affect

any area in the digestive tract. It is suspected to be an autoimmune disease wherein

immune system attacks the tissues and cells of gastrointestinal tract, leading to

inflammation.

Endometriosis

Endometriosis is a gynecological condition in which the endometrium abnormally

grows outside the uterus. In this estrogen dependent disease, endometrium usually

grows on ovaries, bowel, or the tissue lining of pelvis.

Follicular

Lymphoma

Follicular lymphoma, specifically a B-cell lymphoma is an indolent (not painful and

slow) form of Non-Hodgkin's Lymphoma (NHL). It originates in the B-cell germinal

centre. It constitutes nearly 30% of total NHL cases. It is the second most common

form of NHL.

Glaucoma

Glaucoma refers to a group of eye diseases, that cause damage to optic nerve,

resulting in vision loss and blindness. In most of the cases, the increased pressure in

the eye damages the optic nerve.

Heart Failure

Heart failure is a condition in which the heart fails to pump sufficient blood to the

body. As a result, other body organs or tissues receive too little blood and oxygen.

This hampers normal functioning of organs leading to serious medical attention.

Hodgkin's

Lymphoma

Hodgkin's Lymphoma is a type of cancer that originates in lymphatic system. The

cancerous cells may multiply in the affected lymph node and further penetrate the

bloodstream affecting various different organs such as liver, lungs and spleen.

Hypothyroidism

Hypothyroidism is a physiological condition in which the thyroid gland fails to

produce optimal quantity of thyroid hormones. As a result, there is a very low level

of the hormone circulating in the body. Hypothyroidism can lead to serious health

complications if untreated.

Long QT

Long QT is a disorder in which abnormal electrical signals are generated in the

heart. Abnormal electric signals generated in the heart further lead to other medical

complications like irregular heartbeat – known as ‘arrhythmia’.

Lung Cancer

Lung cancer is a type of cancer, which starts in the lungs. There are two major types

of lung cancers, commonly known as small cell lung cancer and non-small cell lung

cancer.

Lupus

Lupus is a systemic autoimmune disease that can affect any part of the body. Lupus

most often harms the heart, joints, skin, lungs, blood vessels, liver, kidneys, and

nervous system.

Major

Depressive

Disorder

Major depressive disorder is a leading cause of psychiatric morbidity and mortality,

worldwide. MDD cases typically suffer from one or more episodes of depression, in

the absence of other conditions such as bipolar disorder and schizophrenia.

Male Pattern

Baldness

Androgenic Alopecia or male pattern baldness is a common hair loss disorder,

predominantly seen in men aged >35-40 years. Hair loss occurs in a predefined

pattern, e.g., thinning over the central part of the scalp (pattern) and/or frontal

hairline retreats.

Melanoma

Melanoma is the most dangerous form of skin cancer and a leading cause of death

due to a skin disease globally. It starts as a malignant tumor in the melanocytes, the

skin cells responsible for the skin pigmentation, eye colour and hair colour.

Migraine

Migraine is a common neurological disorder, with majority of the affected individuals

complaining of recurrent/episodic headache attacks (lasts 4-72 hours).

Multiple

Sclerosis

Multiple Sclerosis is a neuro-immunological disease, where nerves of the brain and

the spinal cord (CNS) are damaged because of degeneration of the myelin sheath, a

protective covering over the nerves, due to inflammation, an autoimmune activity.

Myocardial

Infarction

Myocardial infarction, commonly known as a heart attack, is the interruption of blood

supply resulting in oxygen shortage to the heart. If left untreated for a long time the

heart cells may die.

Osteoarthritis

Osteoarthritis is also known as degenerative arthritis of one or more joints. It

commonly affects hands, feet, spine, and large weight-bearing joints (hips and

knees). However, it is also known to occur at any joint in the body. It is most

commonly seen in older people.

Ovarian Cancer

Ovarian cancer is a type of gynecological/reproductive cancer that affects the

ovaries. It is the fifth most common cancer in women.

Pancreatic

Cancer

Pancreatic cancer is a type of cancer that develops in the tissues of pancreas. It is the

fourth common cancer to affect people worldwide.

Parkinson's

Disease

Parkinson’s disease is a neuro-degenerative brain disorder that leads to tremors

and difficulty in walking, movement, and coordination. Parkinson's disease occurs

when the nerve cells in the brain that make dopamine are slowly destroyed.

Prostate Cancer

Prostate cancer is a type of cancer that develops in the prostate glands. It is one of

the highly inheritable neoplastic conditions in the world.

Psoriasis

Psoriasis is a chronic inflammatory disease that affects skin and joints. Here, the

immune system sends signals to skin cells, which grow too quickly, forming thick,

white, silvery or red patches of skin. In psoriasis, new skin cells move to the surface

in days rather than the usual 4 weeks.

Renal Cell

Carcinoma

Renal cell carcinoma is a cancer that affects the lining of small tubules in the kidney.

It is the most common type of kidney cancer, accounting for 90-95% of kidney

cancers. It is more common in men of 50-70 years.

Restless Legs

Syndrome

Restless Legs Syndrome (RLS) is a sensorimotor disorder, characterized by

unpleasant sensation in the legs (or) uncontrollable urges to move them

(occasionally in hands as well). It is often circadian (symptoms prevail in the evening/

around bedtime).

Rheumatoid

Arthritis

Rheumatoid Arthritis is a chronic autoimmune disease, where immune system attacks

one’s own tissues. It is characterized by inflammation of joints (wrists, knees and

ankles) and the surrounding connective tissues and muscles. It is a systemic disease,

as it can affect multiple other organs in the body.

Schizophrenia

Schizophrenia is a neuro cognitive chronic psychiatric disorder characterized by

severe emotional imbalances and regressive behavior. The person experiences

delusions or hallucinations that are not triggered by stimulus. Disorganized speech,

thought and disturbed behavior are few prominent symptoms.

Sudden Cardiac

Arrest

Sudden Cardiac Arrest (SCA) is a medical condition, where the functioning of the

heart stops abruptly. As a result, the heart ceases to pump blood for other organs

of the body.

Testicular

Cancer

Testicular cancer is a relatively rare form of cancer that affects testicles, which are

part of the male reproductive system. Lumps, swelling or pain in groin area and

testicles are common symptoms of testicular cancer. A feeling of heaviness in the

lower abdomen is seen in few people.

Thyroid Cancer

Thyroid cancer is an uncommon type of cancer caused due to abnormality in the

cells of thyroid gland. Like other thyroid gland related disorders which occur more

frequently in females, thyroid cancer is over 2 times more common in women than in

men.

Type 1 Diabetes

Type 1 diabetes mellitus, previously known as juvenile diabetes, is a chronic

autoimmune disease resulting in destruction of insulin producing beta cells of

pancreas.

Type 2 Diabetes

Type 2 diabetes or non insulin-responsive or dependent diabetes mellitus is the

most common form of diabetes constituting 90% of the diabetic population and a

chronic (lifelong) metabolic disorder, marked by high levels of sugar in the blood.

Ulcerative

Colitis Ulcerative colitis is a type of chronic inflammatory disease characterized by

ulcers in

the inner lining of large intestine.

Vitiligo Vitiligo is an autoimmune disorder wherein melanocytes are self destroyed and

result in depigmentation of the skin and hair, in patches (milky white in colour).

Inherited Conditions

Conditions DESCRIPTION

G6PD

Deficiency

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked recessive

condition prevalent across the globe with nearly 400 million people affected.

Phenylketonuria

Phenylketonuria (PKU) is a rare genetic disorder in which the metabolism of amino

acid phenyl alanine is affected. It is an autosomal recessive abnormality as it

manifests only if both the parents are carriers of mutant alleles.

Drugs

Drugs DESCRIPTION 5FU An anticancer drug for treatment of different cancers.

Abacavir

An antiviral drug given in combination with other antiretroviral drugs for the

treatment of human immunodeficiency viral (HIV) infection.

Aspirin An analgesic, antipyretic, anti-inflammatory or antiplatelet agent.

Clopidogrel

An anti-platelet drug, inhibiting platelet aggregation and preventing blood clot

formation in the body.

Flucloxacillin An antibiotic drug for treating bacterial infections.

Metformin An anti-diabetic drug, to control blood sugar levels in type -2 diabetic patients.

Thiopurines

A chemotherapeutic drug in treatment of cancers or as immunosuppressant drug in

treating auto-immune disorders.

Simvastatin A lipid lowering drug recommended for prevention of coronary heart disease.

Warfarin An anticoagulant drug to treat heart attack and stroke.

INTERPRETATION: What do we do with your DNA When we receive your sample, the first thing we do is to isolate and extract your DNA from the deposited sample. The extracted DNA is your genetic component and is used by us to identify potentially hazardous markers in your DNA, which have proven association with health conditions we cover. The markers we look for in your DNA are called SNPs or single nucleotide polymorphisms (explained below) and these are selected by our scientists after stringent scrutiny of their association for a given health condition. What is genetic information? Genome is the genetic content or hereditary information of an organism, which is made up of DNA (Deoxyribonucleic Acid) in humans and other higher organisms. DNA is made up of four bases Adenine, Thymine Guanine and Cytosine designated by four letters A, T, G, C, respectively. Although the genome of all the humans is almost same, a minor difference exists among individuals. This difference, which is called genetic variation is responsible for unique phenotype (appearance, e.g., color of skin/eyes, type of hair (curly, smooth), etc.) and difference in the health of each individual. In most of the cases, this difference or variation is passed on to the next generation (inheritance), which confers disease susceptibility in the offspring. UNDERSTANDING YOUR RESULTS Relative Risk Relative Risk (RR) is the probability of an individual with a SNP developing a disease relative to an individual without that SNP developing the disease. RR =P(disease with SNP) / P(disease without SNP) RR ~1 -association between SNP and disease unlikely to exist. RR > 1 -increased risk of disease among those with that SNP. RR < 1 -decreased risk of disease among those with that SNP. Your Risk Assessment It is an estimate of the likelihood of developing a medical condition. In other words, it indicates the probability threat value of your mutation leading to health condition. For Example: Your lifetime risk: 6.8% What it means: Individuals with your genetic variants are estimated to develop this condition in 6.8 out of every 100 persons. These results indicate your odds of developing this condition. Your average lifetime risk: 8% What it means: Individuals from the average population are estimated to develop this condition in 8 out of every 100 persons. Note: This test looks for most common and already-proven variants associated with a condition and does not screen for all variations. There may be other associated markers/variants not screened here. Single Nucleotide Polymorphism (SNP)

Single nucleotide polymorphism or SNP is a type of genetic variation, where in a single letter difference occurs in the DNA sequence of an individual when compared to others. Example: Sequence 1: ----AGCCTAATGGGC----

Sequence 2: ----AGCCTAAGGGGC---- Here, in the given example, the first sequence differs from the second sequence only by a single letter (nucleotideT/G). This single letter variation affects many phenotypic traits, disease susceptibility/ resistance, response to drugs, chemicals, radiation, etc. SNP Genotyping Genotype is the genetic makeup of an organism, and genotyping (process by which the genotype sequence is decoded) is done to understand difference in the genetic makeup between different individuals. SNP genotyping helps to analyze the SNPs present in an individual. What your report is and what it is not This report is only based on your genes and not on any other information you share. The report what we provide you is not diagnostic in nature and should not be considered as one. What we report is your genetic predisposition towards any particular health condition. If you are reported to be on the higher risk for any of the health condition we cover, it does not mean that you have or you will contract the health condition and the same applies if you are reported to be on the lower risk. When a person develops a health condition it may be due to their genetic predisposition, lifestyle, exposure to hazardous material, environmental conditions and many more. What we provide you should help in assessing your health status on genetic level and making the right choices for your health. GENETIC PREDISPOSITION DOES NOT MEAN PREDETERMINATION

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Dummy Age/sex : xxxY / M 00000000 … : Dummy Age/sex : xxxY / M Lab No : 00000000 Rep centre : xxxxxxxxxxxxxxxxxxxxx Ref by : xxxxxxxxxxxxxxxxxxxxx Rec. Date : xx/xx/xxxx Rep Date